The spinal cord links the brain and the peripheral nervous system and has important sensory and motor functions.Impairments in the spinal cord occur in different diseases,such as spinal cord injury,multiple sclerosis,...The spinal cord links the brain and the peripheral nervous system and has important sensory and motor functions.Impairments in the spinal cord occur in different diseases,such as spinal cord injury,multiple sclerosis,pain,motor neuron diseases,and neurodegenerative diseases.Imaging of the spinal cord has been challenging,partly due to its small size and deep anatomical location.Additionally,in an animal model,motion artifacts further influence the in vivo imaging quality of the spinal cord.Recent advances have pushed boundaries for in vivo imaging in living animals(even behaving animals).展开更多
Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include...Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Background and purpose: Lifelong endurance exercise is generally associated with cardiovascular health benefits.However, recent studies suggest that prolonged high-volume training may contribute to coronary atheroscle...Background and purpose: Lifelong endurance exercise is generally associated with cardiovascular health benefits.However, recent studies suggest that prolonged high-volume training may contribute to coronary atherosclerosis,even in athletes with low traditional cardiovascular risk. This case report aims to explore the cardiovascular status of a master endurance athlete with an exceptionally high lifetime training volume, in light of recent concerns raised in the literature.Methods: We present the case of a 60-year-old recreational male marathon runner with no history of cardiovascular disease, who completed over 500 marathons between the ages of 30 and 60 years, covering ~127 000-km running. In 2024 alone, he completed 60 marathons. Cardiovascular evaluation included clinical risk assessment and coronary computed tomography angiography(CTCA).Results: The runner was asymptomatic, had a low ESC-SCORE2(3.3%), a favorable lipid profile, and normal levels of high-sensitivity C-reactive protein and lipoprotein(a). CTCA revealed no evidence of calcified, mixed, or non-calcified coronary plaques.Conclusions: This case highlights that some master athletes may demonstrate resilience to coronary atherosclerosis despite decades of high training volume. In low-risk individuals, prolonged endurance training alone may not necessarily lead to coronary artery disease, emphasizing the need for individualized cardiovascular screening strategies.展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
AIM:To evaluate the short-term efficacy of XEN45 Gel Stent(XEN)implantation for primary open angle glaucoma(POAG)and pseudoexfoliation(PEX)glaucoma across two university eye clinics,aiming to assess the impact of vary...AIM:To evaluate the short-term efficacy of XEN45 Gel Stent(XEN)implantation for primary open angle glaucoma(POAG)and pseudoexfoliation(PEX)glaucoma across two university eye clinics,aiming to assess the impact of varying center-specific protocols during the first postoperative year.METHODS:We retrospectively examined 282 patients(183 in center 1,99 in center 2),who underwent XEN microstent implantation for uncontrolled POAG or PEX glaucoma.Parameters including intraocular pressure(IOP),IOP-lowering medication count,best corrected visual acuity(BCVA),and postoperative complications were evaluated over 12mo.RESULTS:Post-implantation,center 1 reported a mean IOP reduction from 25.3±7.4 to 14.1±4.7 mm Hg(P<0.01)and a decrease in IOP-lowering medications from 3.2±1.2 to 1.0±1.3(P<0.01).Center 2 observed a similar reduction from 24.4±6.5 to 15.1±5.5 mm Hg(P<0.01)and medication decrease from 3.0±1.1 to 1.2±1.0(P<0.01).BCVA remained stable in both cohorts.The most common complications were hypotony(center 1:32;center 2:20)and choroidal detachment(center 1:22,center 2:15),with nearly identical needling rates(40% in center 1,41% in center 2).CONCLUSION:XEN implantation yields consistent reductions in IOP and medication use across different centers using comparable surgical and postoperative treatment regime.These findings underscore XEN’s shortterm effectiveness and suggest standardizable outcomes regardless of exact surgical procedure or treatment differences.展开更多
Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regul...Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha(SIRPα)on macrophages and dendritic cells(DCs).Although early enthusiasm drove broad clinical development,recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential.The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations.Clinical challenges,including anemia,thrombocytopenia,suboptimal pharmacokinetics,and limited single-agent efficacy,underscore the need to develop safer,more selective approaches.Emerging next-generation strategies,such as SIRPα-directed agents,bispecific antibodies,and conditionally active therapeutics,are designed to enhance safety and tumor selectivity and reduce systemic toxicity.In addition,spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations,including with“eat-me”signals(e.g.,calreticulin[CALR])orDNA damage response therapies(e.g.,poly(ADP-ribose)polymerase[PARP]inhibitors).Rather than signaling failure,these developments underscore the need for precision,context-specific applications,and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.展开更多
AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) a...AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology. RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis. CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.展开更多
AIM To compare KAI1 in cancer of papilla ofVater and pancreas to evaluate whether there aredifferences in biologic behavior which mightaccount for prognosis.METHODS We compared the expression in 24papillay and 29 panc...AIM To compare KAI1 in cancer of papilla ofVater and pancreas to evaluate whether there aredifferences in biologic behavior which mightaccount for prognosis.METHODS We compared the expression in 24papillay and 29 pancreatic cancers usingNorthern blot analysis,immunochemical assayand in situ hybridization,and investigatedwhether early diagnosis or molecular differencespredict the outcome in these tumor entities.RESULTS By Northern blot analysis there is nostatistical difference of KAI1 levels in normaland cancerous papilla.No association betweenKAI1 mRNA expression and tumor stage or tumordifferentiation was found in the tumors.Byimmunohistochemical assay,KAI1 staining incytoplasm of papillary cancer cells was similarto that of normal papillary cells.By in situhybridization,the results of KAI1 mRNAexpression in normal and cancerous papilla weresimilar to those with immunohistochemicalassay.The normal and cancerous pancreastissues were also analyzed by the methods usedin papillary samples.CONCLUSION Although the biologic roles of KAI1 have not been clarified, our results suggest that KAI1 may restrict the progression of malignant papillary cancer, but its expression might not have any effect on the characteristics of papillary tumor, whereas by the analysis of KAl1 gene, its reduced expression is closely related to the progression and metastases of pancreatic cancer.展开更多
Liver transplantation represents the only curative option for patients with endstage liver disease,fulminant hepatitis and advanced hepatocellular carcinoma.Even though major advances in transplantation in the last de...Liver transplantation represents the only curative option for patients with endstage liver disease,fulminant hepatitis and advanced hepatocellular carcinoma.Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period,long-term survival is hampered by the lack of improvement in survival in the late post transplantation period(over 5 years after transplantation).The main etiologies for late mortality are malignancies and cardiovascular complications.The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components(arterial hypertension,dyslipidemia,obesity,renal injury,etc.).These comorbidities result from a combination of pre-liver transplant features,immunosuppressive agent side-effects,changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle.In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation,as well as proposing management strategies.展开更多
AIM: To investigate age-and gender-related differences in non-culprit versus culprit coronary vessels assessed with virtual histology intravascular ultrasound (VH-IVUS). METHODS: In 390 patients referred for coronary ...AIM: To investigate age-and gender-related differences in non-culprit versus culprit coronary vessels assessed with virtual histology intravascular ultrasound (VH-IVUS). METHODS: In 390 patients referred for coronary angiography to a single center (Luzerner Kantonsspital, Switzerland) between May 2007 and January 2011, 691 proximal vessel segments in left anterior descending, circumflex and/or right coronary arteries were imaged by VH-IVUS. Plaque burden and plaque composition(fibrous, fibro-fatty, necrotic core and dense calcium volumes) were analyzed in 3 age tertiles, according to gender and separated for vessels containing non-culprit or culprit lesions. To classify as vessel containing a culprit lesion, the patient had to present with an acute coronary syndrome, and the VH-IVUS had to be performed in a vessel segment containing the culprit lesion according to conventional coronary angiography. RESULTS: In non-culprit vessels the plaque burden increased significantly with aging (in men from 37% ± 12% in the lowest to 46% ± 10% in the highest age tertile, P < 0.001; in women from 30% ± 9% to 40% ± 11%, P < 0.001); men had higher plaque burden than women at any age (P < 0.001 for each of the 3 age tertiles). In culprit vessels of the lowest age tertile, plaque burden was significantly higher than that in non- culprit vessels (in men 48% ± 6%, P < 0.001 as compared to non-culprit vessels; in women 44% ± 18%, P = 0.004 as compared to non-culprit vessels). Plaque burden of culprit vessels did not significantly change during aging (plaque burden in men of the highest age tertile 51% ± 9%, P = 0.523 as compared to lowest age tertile; in women of the highest age tertile 49% ± 8%, P = 0.449 as compared to lowest age tertile). In men, plaque morphology of culprit vessels became increasingly rupture-prone during aging (increasing percentages of necrotic core and dense calcium), whereas plaque morphology in non-culprit vessels was less rupture-prone and remained constant during aging. In women, necrotic core in non-culprit vessels was very low at young age, but increased during aging resulting in a plaque morphology that was very similar to men. Plaque morphology in culprit vessels of young women and men was similar. CONCLUSION: This study provides evidence that age-and gender-related differences in plaque burden and plaque composition significantly depend on whether the vessel contained a non-culprit or culprit lesion.展开更多
BACKGROUND Inflammatory myofibroblastic tumors of the liver(IMTL)are extremely rare neoplasms and very little is known about their clinical presentation,pathogenesis,and biological behavior.Due to their absolute rarit...BACKGROUND Inflammatory myofibroblastic tumors of the liver(IMTL)are extremely rare neoplasms and very little is known about their clinical presentation,pathogenesis,and biological behavior.Due to their absolute rarity,it is almost impossible to obtain a definite diagnosis without histological examination.Because of their intermediate biological behavior with the risk for local recurrence and metastases,surgical resection is recommend whenever IMTL is suspect.CASE SUMMARY We herein present a case of an otherwise healthy 32-year-old woman who presented with intermittent fever,unclear anemia,malaise and right flank pain 4 mo postpartum.The liver mass in segment IVa/b was highly FDG avid in the positron emission tomography-computed tomography.Hepatic resection was performed achieving a negative resection margin and an immediate resolution of all clinical symptoms.Histological analysis diagnosed the rare finding of an inflammatory myofibroblastic tumor of the liver and revealed cytoplasmic anaplastic lymphoma kinase expression by immunohistochemistry.Twelve months follow-up magnetic resonance imaging showed no recurrence and no metastases in the fully recovered patient.CONCLUSION IMTLs are extremely rare and difficult to diagnose.Due to their intermediate biological behavior,surgical resection should be perform whenever feasible and patients should be followed-up in order to detect recurrence and metastasis as early as possible.展开更多
We report the exceptional case of hepatocellular carcinoma in a non-cirrhotic patient, whose Wilson's disease was diagnosed at the unusual age of 58 years. The liver histology revealed macrovesicular steatosis wit...We report the exceptional case of hepatocellular carcinoma in a non-cirrhotic patient, whose Wilson's disease was diagnosed at the unusual age of 58 years. The liver histology revealed macrovesicular steatosis with fibrosis, but no cirrhosis. The disease was treated with D-penicillamine for 3 years until acute discomfort in the right upper quadrant led to detection of multifocal hepatocellular carcinoma, which was successfully resected. The histological examination confirmed the malignant nature of the 4 lesions, which were classified according to Edmondson and Steiner as poorly differentiated hepatocellular carcinoma grade 3. The non-tumoral parenchyma showed 80% steatosis with ballooned cells, lobular inflammation, septal fibrosis but no cirrhosis. Hepatocellular carcinoma is rare in Wilson's disease, especially in the absence of cirrhosis. The literature's 28 published cases are reviewed and the contributory role of copper in the hepatocarcinogenic process is discussed.展开更多
BACKGROUND Perinatal complications may result in life-long morbidities,among which cerebral palsy(CP)is the most severe motor disability.Once developed,CP is a nonprogressive disease with a prevalence of 1-2 per 1000 ...BACKGROUND Perinatal complications may result in life-long morbidities,among which cerebral palsy(CP)is the most severe motor disability.Once developed,CP is a nonprogressive disease with a prevalence of 1-2 per 1000 live births in developed countries.It demands an extensive and multidisciplinary care.Therefore,it is a challenge for our health system and a burden for patients and their families.Recently,stem cell therapy emerged as a promising treatment option and raised hope in patients and their families.AIM The aim is to evaluate the efficacy and safety of stem cell treatment in children with CP using a systematic review and meta-analysis METHODS We performed a systematic literature search on PubMed and EMBASE to find randomized controlled clinical trials(RCT)investigating the effect of stem cell transplantation in children with CP.After the review,we performed a randomeffects meta-analysis focusing on the change in gross motor function,which was quantified using the gross motor function measure.We calculated the pooled standardized mean differences of the 6-and/or 12-mo-outcome by the method of Cohen.We quantified the heterogeneity using the I-squared measure.RESULTS We identified a total of 8 RCT for a qualitative review.From the initially selected trials,5 met the criteria and were included in the meta-analysis.Patients’population ranged from 0.5 up to 35 years(n=282).We detected a significant improvement in the gross motor function with a pooled standard mean difference of 0.95(95%confidence interval:0.13-1.76)favoring the stem cell group and a high heterogeneity(I2=90.1%).Serious adverse events were rare and equally distributed among both intervention and control groups.CONCLUSION Stem cell therapy for CP compared with symptomatic standard care only,shows a significant positive effect on the gross motor function,although the magnitude of the improvement is limited.Short-term safety is present and further highquality RCTs are needed.展开更多
AIM： To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer （CRC） patients.（/7 = 53） and in patients who did not receive FOLFOX ch...AIM： To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer （CRC） patients.（/7 = 53） and in patients who did not receive FOLFOX chemotherapy prior to liver surgery （n = 29）. RESULTS： Of the 53 patients who received FOLFOX, time to liver surgery was n〈 1 mo in 14 patients, 〈 1 year in 22 patients and 〉 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein ex- pression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ~〈 12 mo before liver surgery （P 〈 0.001） in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treat- ment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION： This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.展开更多
Autophagy is a highly regulated catabolic process in which superfluous,damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates d...Autophagy is a highly regulated catabolic process in which superfluous,damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates during basal or stressed conditions.Autophagy is a bimodal process with a context dependent role in the initiation and the development of cancers.For instance,autophagy provides an adaptive response to cancer stem cells to survive metabolic stresses,by influencing disease propagation via modulation of essential signaling pathways or by promoting resistance to chemotherapeutics.Autophagy has been implicated in a cross talk with apoptosis.Understanding the complex interactions provides an opportunity to improve cancer therapy and the clinical outcome for the cancer patients.In this review,we provide a comprehensive view on the current knowledge on autophagy and its role in cancer cells with a particular focus on cancer stem cell homeostasis.展开更多
Tumors consist of a mixture of heterogeneous cell types. Cancer stem cells(CSCs) are a minor sub-population within the bulk cancer fraction which has been foundto reconstitute and propagate the disease and to be frequ...Tumors consist of a mixture of heterogeneous cell types. Cancer stem cells(CSCs) are a minor sub-population within the bulk cancer fraction which has been foundto reconstitute and propagate the disease and to be frequently resistant to chemotherapy, irradiation, cytotoxic drugs and probably also against immune attack. CSCs are considered as the seeds of tumor recurrence, driving force of tumorigenesis and metastases. This underlines the urgent need for innovative methods to identify and target CSCs. However, the role and existence of CSCs in therapy resistance and cancer recurrence remains a topic of intense debate. The underlying biological properties of the tumor stem cells are extremely dependent on numerous signals, and the targeted inhibition of these stem cell signaling pathways is one of the promising approaches of the new antitumor therapy approaches. This perspective review article summarizes the novel methods of tracing CSCs and discusses the hallmarks of CSC identification influenced by the microenvironment or by having imperfect detection markers. In addition, explains the known molecular mechanisms of therapy resistance in CSCs as reliable and clinically predictive markers that could enable the use of new targeted antitumor therapy in the sense of personalized medicine.展开更多
文摘The spinal cord links the brain and the peripheral nervous system and has important sensory and motor functions.Impairments in the spinal cord occur in different diseases,such as spinal cord injury,multiple sclerosis,pain,motor neuron diseases,and neurodegenerative diseases.Imaging of the spinal cord has been challenging,partly due to its small size and deep anatomical location.Additionally,in an animal model,motion artifacts further influence the in vivo imaging quality of the spinal cord.Recent advances have pushed boundaries for in vivo imaging in living animals(even behaving animals).
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN)。
文摘Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
文摘Background and purpose: Lifelong endurance exercise is generally associated with cardiovascular health benefits.However, recent studies suggest that prolonged high-volume training may contribute to coronary atherosclerosis,even in athletes with low traditional cardiovascular risk. This case report aims to explore the cardiovascular status of a master endurance athlete with an exceptionally high lifetime training volume, in light of recent concerns raised in the literature.Methods: We present the case of a 60-year-old recreational male marathon runner with no history of cardiovascular disease, who completed over 500 marathons between the ages of 30 and 60 years, covering ~127 000-km running. In 2024 alone, he completed 60 marathons. Cardiovascular evaluation included clinical risk assessment and coronary computed tomography angiography(CTCA).Results: The runner was asymptomatic, had a low ESC-SCORE2(3.3%), a favorable lipid profile, and normal levels of high-sensitivity C-reactive protein and lipoprotein(a). CTCA revealed no evidence of calcified, mixed, or non-calcified coronary plaques.Conclusions: This case highlights that some master athletes may demonstrate resilience to coronary atherosclerosis despite decades of high training volume. In low-risk individuals, prolonged endurance training alone may not necessarily lead to coronary artery disease, emphasizing the need for individualized cardiovascular screening strategies.
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
基金Funded by the Open Access Publishing Fund of Leipzig University supported by the German Research Foundation within the program Open Access.
文摘AIM:To evaluate the short-term efficacy of XEN45 Gel Stent(XEN)implantation for primary open angle glaucoma(POAG)and pseudoexfoliation(PEX)glaucoma across two university eye clinics,aiming to assess the impact of varying center-specific protocols during the first postoperative year.METHODS:We retrospectively examined 282 patients(183 in center 1,99 in center 2),who underwent XEN microstent implantation for uncontrolled POAG or PEX glaucoma.Parameters including intraocular pressure(IOP),IOP-lowering medication count,best corrected visual acuity(BCVA),and postoperative complications were evaluated over 12mo.RESULTS:Post-implantation,center 1 reported a mean IOP reduction from 25.3±7.4 to 14.1±4.7 mm Hg(P<0.01)and a decrease in IOP-lowering medications from 3.2±1.2 to 1.0±1.3(P<0.01).Center 2 observed a similar reduction from 24.4±6.5 to 15.1±5.5 mm Hg(P<0.01)and medication decrease from 3.0±1.1 to 1.2±1.0(P<0.01).BCVA remained stable in both cohorts.The most common complications were hypotony(center 1:32;center 2:20)and choroidal detachment(center 1:22,center 2:15),with nearly identical needling rates(40% in center 1,41% in center 2).CONCLUSION:XEN implantation yields consistent reductions in IOP and medication use across different centers using comparable surgical and postoperative treatment regime.These findings underscore XEN’s shortterm effectiveness and suggest standardizable outcomes regardless of exact surgical procedure or treatment differences.
文摘Cluster of differentiation 47(CD47),an immune checkpoint commonly referred to as the“don’t eat me”signal,plays a pivotal role in tumor immune evasion by inhibiting phagocytosis through interaction with signal regulatory protein alpha(SIRPα)on macrophages and dendritic cells(DCs).Although early enthusiasm drove broad clinical development,recent discontinuations of major CD47-targeted programs have prompted re-evaluation of its therapeutic potential.The purpose of this commentary is to contextualize the setbacks observed with first-generation CD47 inhibitors and to highlight strategies aimed at overcoming their limitations.Clinical challenges,including anemia,thrombocytopenia,suboptimal pharmacokinetics,and limited single-agent efficacy,underscore the need to develop safer,more selective approaches.Emerging next-generation strategies,such as SIRPα-directed agents,bispecific antibodies,and conditionally active therapeutics,are designed to enhance safety and tumor selectivity and reduce systemic toxicity.In addition,spatial profiling and biomarker-driven patient selection are advancing toward guiding rational therapeutic combinations,including with“eat-me”signals(e.g.,calreticulin[CALR])orDNA damage response therapies(e.g.,poly(ADP-ribose)polymerase[PARP]inhibitors).Rather than signaling failure,these developments underscore the need for precision,context-specific applications,and adaptive trial designs to realize the durable therapeutic promise of CD47 blockade in cancer immunotherapy.
文摘AIM: To examine the role of p38 during acute experimental cerulein pancreatitis. METHODS: Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347) and/or a specific p38 inhibitor (SB203580) and pancreatic stress kinase activity was determined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology. RESULTS: JNK inhibition with CEP1347 ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580 aggravated pancreatitis with higher trypsin levels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation. Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis. CONCLUSION: Stress kinases modulate pancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.
文摘AIM To compare KAI1 in cancer of papilla ofVater and pancreas to evaluate whether there aredifferences in biologic behavior which mightaccount for prognosis.METHODS We compared the expression in 24papillay and 29 pancreatic cancers usingNorthern blot analysis,immunochemical assayand in situ hybridization,and investigatedwhether early diagnosis or molecular differencespredict the outcome in these tumor entities.RESULTS By Northern blot analysis there is nostatistical difference of KAI1 levels in normaland cancerous papilla.No association betweenKAI1 mRNA expression and tumor stage or tumordifferentiation was found in the tumors.Byimmunohistochemical assay,KAI1 staining incytoplasm of papillary cancer cells was similarto that of normal papillary cells.By in situhybridization,the results of KAI1 mRNAexpression in normal and cancerous papilla weresimilar to those with immunohistochemicalassay.The normal and cancerous pancreastissues were also analyzed by the methods usedin papillary samples.CONCLUSION Although the biologic roles of KAI1 have not been clarified, our results suggest that KAI1 may restrict the progression of malignant papillary cancer, but its expression might not have any effect on the characteristics of papillary tumor, whereas by the analysis of KAl1 gene, its reduced expression is closely related to the progression and metastases of pancreatic cancer.
文摘Liver transplantation represents the only curative option for patients with endstage liver disease,fulminant hepatitis and advanced hepatocellular carcinoma.Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period,long-term survival is hampered by the lack of improvement in survival in the late post transplantation period(over 5 years after transplantation).The main etiologies for late mortality are malignancies and cardiovascular complications.The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components(arterial hypertension,dyslipidemia,obesity,renal injury,etc.).These comorbidities result from a combination of pre-liver transplant features,immunosuppressive agent side-effects,changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle.In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation,as well as proposing management strategies.
基金Supported by Swiss Heart Foundation, Bern, Switzerlandthe Swiss National Science Foundation, No. 310000-118468/1, Bern,Switzerlandthe Kamillo-Eisner Foundation, Hergiswil,Switzerland
文摘AIM: To investigate age-and gender-related differences in non-culprit versus culprit coronary vessels assessed with virtual histology intravascular ultrasound (VH-IVUS). METHODS: In 390 patients referred for coronary angiography to a single center (Luzerner Kantonsspital, Switzerland) between May 2007 and January 2011, 691 proximal vessel segments in left anterior descending, circumflex and/or right coronary arteries were imaged by VH-IVUS. Plaque burden and plaque composition(fibrous, fibro-fatty, necrotic core and dense calcium volumes) were analyzed in 3 age tertiles, according to gender and separated for vessels containing non-culprit or culprit lesions. To classify as vessel containing a culprit lesion, the patient had to present with an acute coronary syndrome, and the VH-IVUS had to be performed in a vessel segment containing the culprit lesion according to conventional coronary angiography. RESULTS: In non-culprit vessels the plaque burden increased significantly with aging (in men from 37% ± 12% in the lowest to 46% ± 10% in the highest age tertile, P < 0.001; in women from 30% ± 9% to 40% ± 11%, P < 0.001); men had higher plaque burden than women at any age (P < 0.001 for each of the 3 age tertiles). In culprit vessels of the lowest age tertile, plaque burden was significantly higher than that in non- culprit vessels (in men 48% ± 6%, P < 0.001 as compared to non-culprit vessels; in women 44% ± 18%, P = 0.004 as compared to non-culprit vessels). Plaque burden of culprit vessels did not significantly change during aging (plaque burden in men of the highest age tertile 51% ± 9%, P = 0.523 as compared to lowest age tertile; in women of the highest age tertile 49% ± 8%, P = 0.449 as compared to lowest age tertile). In men, plaque morphology of culprit vessels became increasingly rupture-prone during aging (increasing percentages of necrotic core and dense calcium), whereas plaque morphology in non-culprit vessels was less rupture-prone and remained constant during aging. In women, necrotic core in non-culprit vessels was very low at young age, but increased during aging resulting in a plaque morphology that was very similar to men. Plaque morphology in culprit vessels of young women and men was similar. CONCLUSION: This study provides evidence that age-and gender-related differences in plaque burden and plaque composition significantly depend on whether the vessel contained a non-culprit or culprit lesion.
文摘BACKGROUND Inflammatory myofibroblastic tumors of the liver(IMTL)are extremely rare neoplasms and very little is known about their clinical presentation,pathogenesis,and biological behavior.Due to their absolute rarity,it is almost impossible to obtain a definite diagnosis without histological examination.Because of their intermediate biological behavior with the risk for local recurrence and metastases,surgical resection is recommend whenever IMTL is suspect.CASE SUMMARY We herein present a case of an otherwise healthy 32-year-old woman who presented with intermittent fever,unclear anemia,malaise and right flank pain 4 mo postpartum.The liver mass in segment IVa/b was highly FDG avid in the positron emission tomography-computed tomography.Hepatic resection was performed achieving a negative resection margin and an immediate resolution of all clinical symptoms.Histological analysis diagnosed the rare finding of an inflammatory myofibroblastic tumor of the liver and revealed cytoplasmic anaplastic lymphoma kinase expression by immunohistochemistry.Twelve months follow-up magnetic resonance imaging showed no recurrence and no metastases in the fully recovered patient.CONCLUSION IMTLs are extremely rare and difficult to diagnose.Due to their intermediate biological behavior,surgical resection should be perform whenever feasible and patients should be followed-up in order to detect recurrence and metastasis as early as possible.
文摘We report the exceptional case of hepatocellular carcinoma in a non-cirrhotic patient, whose Wilson's disease was diagnosed at the unusual age of 58 years. The liver histology revealed macrovesicular steatosis with fibrosis, but no cirrhosis. The disease was treated with D-penicillamine for 3 years until acute discomfort in the right upper quadrant led to detection of multifocal hepatocellular carcinoma, which was successfully resected. The histological examination confirmed the malignant nature of the 4 lesions, which were classified according to Edmondson and Steiner as poorly differentiated hepatocellular carcinoma grade 3. The non-tumoral parenchyma showed 80% steatosis with ballooned cells, lobular inflammation, septal fibrosis but no cirrhosis. Hepatocellular carcinoma is rare in Wilson's disease, especially in the absence of cirrhosis. The literature's 28 published cases are reviewed and the contributory role of copper in the hepatocarcinogenic process is discussed.
文摘BACKGROUND Perinatal complications may result in life-long morbidities,among which cerebral palsy(CP)is the most severe motor disability.Once developed,CP is a nonprogressive disease with a prevalence of 1-2 per 1000 live births in developed countries.It demands an extensive and multidisciplinary care.Therefore,it is a challenge for our health system and a burden for patients and their families.Recently,stem cell therapy emerged as a promising treatment option and raised hope in patients and their families.AIM The aim is to evaluate the efficacy and safety of stem cell treatment in children with CP using a systematic review and meta-analysis METHODS We performed a systematic literature search on PubMed and EMBASE to find randomized controlled clinical trials(RCT)investigating the effect of stem cell transplantation in children with CP.After the review,we performed a randomeffects meta-analysis focusing on the change in gross motor function,which was quantified using the gross motor function measure.We calculated the pooled standardized mean differences of the 6-and/or 12-mo-outcome by the method of Cohen.We quantified the heterogeneity using the I-squared measure.RESULTS We identified a total of 8 RCT for a qualitative review.From the initially selected trials,5 met the criteria and were included in the meta-analysis.Patients’population ranged from 0.5 up to 35 years(n=282).We detected a significant improvement in the gross motor function with a pooled standard mean difference of 0.95(95%confidence interval:0.13-1.76)favoring the stem cell group and a high heterogeneity(I2=90.1%).Serious adverse events were rare and equally distributed among both intervention and control groups.CONCLUSION Stem cell therapy for CP compared with symptomatic standard care only,shows a significant positive effect on the gross motor function,although the magnitude of the improvement is limited.Short-term safety is present and further highquality RCTs are needed.
文摘AIM： To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer （CRC） patients.（/7 = 53） and in patients who did not receive FOLFOX chemotherapy prior to liver surgery （n = 29）. RESULTS： Of the 53 patients who received FOLFOX, time to liver surgery was n〈 1 mo in 14 patients, 〈 1 year in 22 patients and 〉 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein ex- pression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ~〈 12 mo before liver surgery （P 〈 0.001） in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treat- ment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION： This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.
文摘Autophagy is a highly regulated catabolic process in which superfluous,damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates during basal or stressed conditions.Autophagy is a bimodal process with a context dependent role in the initiation and the development of cancers.For instance,autophagy provides an adaptive response to cancer stem cells to survive metabolic stresses,by influencing disease propagation via modulation of essential signaling pathways or by promoting resistance to chemotherapeutics.Autophagy has been implicated in a cross talk with apoptosis.Understanding the complex interactions provides an opportunity to improve cancer therapy and the clinical outcome for the cancer patients.In this review,we provide a comprehensive view on the current knowledge on autophagy and its role in cancer cells with a particular focus on cancer stem cell homeostasis.
文摘Tumors consist of a mixture of heterogeneous cell types. Cancer stem cells(CSCs) are a minor sub-population within the bulk cancer fraction which has been foundto reconstitute and propagate the disease and to be frequently resistant to chemotherapy, irradiation, cytotoxic drugs and probably also against immune attack. CSCs are considered as the seeds of tumor recurrence, driving force of tumorigenesis and metastases. This underlines the urgent need for innovative methods to identify and target CSCs. However, the role and existence of CSCs in therapy resistance and cancer recurrence remains a topic of intense debate. The underlying biological properties of the tumor stem cells are extremely dependent on numerous signals, and the targeted inhibition of these stem cell signaling pathways is one of the promising approaches of the new antitumor therapy approaches. This perspective review article summarizes the novel methods of tracing CSCs and discusses the hallmarks of CSC identification influenced by the microenvironment or by having imperfect detection markers. In addition, explains the known molecular mechanisms of therapy resistance in CSCs as reliable and clinically predictive markers that could enable the use of new targeted antitumor therapy in the sense of personalized medicine.
