BACKGROUND Nosocomial fever of unknown origin(nFUO)is a frequent and challenging diagnostic entity,encompassing diverse infectious and non-infectious etiologies.Timely identification is crucial,yet evidence on the dia...BACKGROUND Nosocomial fever of unknown origin(nFUO)is a frequent and challenging diagnostic entity,encompassing diverse infectious and non-infectious etiologies.Timely identification is crucial,yet evidence on the diagnostic accuracy of commonly employed sepsis screening tools and biomarkers remains sparse.We hypothesized that these tools and biomarkers measured at fever onset could distinguish infectious from non-infectious causes of nFUO in critically ill adults.AIM To evaluate the diagnostic utility of sepsis tools and biomarkers in identifying infectious causes of nFUO.METHODS This prospective observational study included patients admitted to the Acute Care Emergency Medicine Unit,Postgraduate Institute of Medical Education and Research,Chandigarh,India(July 2023 to December 2024).nFUO was defined by Durack and Street criteria.Diagnostic performance of sepsis screening tools(systemic inflammatory response syndrome,Sequential Organ Failure Assessment,quick Sequential Organ Failure Assessment,National Early Warning Score,and Modified Early Warning Score)and biomarkers[procalcitonin(PCT),C-reactive protein(CRP)]at fever onset was assessed using receiver operating characteristic curve analysis.RESULTS Of 80 cases(mean age 42.9±16.5 years;80% male),42.5% had infectious causes,38.7% non-infectious,and 18.8% remained undiagnosed.Pneumonia(26.2%)and bloodstream infections(11.2%)were the most common infectious etiologies,while central fever and thrombophlebitis(each 7.5%)were predominant among non-infectious causes.Sepsis tools showed poor diagnostic accuracy,with area under the receiver operating characteristic curve(AUC)values close to 0.5.PCT demonstrated modest performance(AUC=0.61;optimal cut-off:0.85μg/L),while CRP was paradoxically higher in non-infectious cases(AUC=0.45).Overall mortality was 20% and was highest among undiagnosed patients(33.3%).Fever duration and hospitalization length were significantly greater in infectious cases.CONCLUSION Sepsis tools,PCT,and CRP have limited utility in identifying infectious causes of nFUO in critically ill adults and should not solely guide initial decision-making.展开更多
Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying m...Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.展开更多
During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like recept...During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like receptors,and nucleotide-binding and oligomerization domain-like receptors.The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons(IFNs),especially IFN-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host.Although these sensors are hardwired to recognize pathogen associated molecular patterns,like viral and bacterial nucleic acids,under unusual physiological conditions,such as excessive cellular stress and increased apoptosis,endogenous self-nucleic acids like DNA,RNA,and mitochondrial DNA are also released.The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders,like systemic lupus erythematosus,psoriasis and to some extent in type 1 diabetes(T1D).This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.展开更多
Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than sub...Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D.Over the past decade and a half,a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease.While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism,a few reports suggest a lack of such association.Pancreatic fat has also been linked with genetic risk of developing T2D,prediabetes,reduced insulin secretion,and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome.With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function,our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved.This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.展开更多
Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparamet...Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.展开更多
Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping ...Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping countries.Methods: A total of 312 first degree relativesbelonging to 80 families of children with TD (group 1)and 40 families of age-matched normal children (group2) were screened by thyroid ultrasonography, serum totalthyroxine (T4) and thyroid stimulating hormone (TSH).Results: Thyroid scintigraphy revealed agenesis in78.7% of the patients, ectopic gland in 15%, and hypoplasiain 6.2%. The mean thyroid volumes were similar in parentsand siblings of both groups. Eight (10.6%) mothers in group1 were identified to have thyroid hypoplasia as comparedwith none in group 2 (P=0.03). Serum TSH was signifi cantlyhigher in group 1 than in group 2 (P=0.004). Sixteen (7.8%)subjects (6 mothers, 5 fathers, and 5 siblings) in group 1were found to have subclinical hypothyroidism as comparedto none in group 2 (P<0.05). Four families were identifiedto have thyroid developmental anomalies and abnormalthyroid functions accounting for 5% of cases of familial TDin our cohort.Conclusions: Thyroid developmental anomalies andthyroid function abnormalities are more frequent in firstdegree relatives of children with TD as compared with acontrol population. These findings suggest that possiblythere is a genetic component of TD in Indian patients.展开更多
文摘BACKGROUND Nosocomial fever of unknown origin(nFUO)is a frequent and challenging diagnostic entity,encompassing diverse infectious and non-infectious etiologies.Timely identification is crucial,yet evidence on the diagnostic accuracy of commonly employed sepsis screening tools and biomarkers remains sparse.We hypothesized that these tools and biomarkers measured at fever onset could distinguish infectious from non-infectious causes of nFUO in critically ill adults.AIM To evaluate the diagnostic utility of sepsis tools and biomarkers in identifying infectious causes of nFUO.METHODS This prospective observational study included patients admitted to the Acute Care Emergency Medicine Unit,Postgraduate Institute of Medical Education and Research,Chandigarh,India(July 2023 to December 2024).nFUO was defined by Durack and Street criteria.Diagnostic performance of sepsis screening tools(systemic inflammatory response syndrome,Sequential Organ Failure Assessment,quick Sequential Organ Failure Assessment,National Early Warning Score,and Modified Early Warning Score)and biomarkers[procalcitonin(PCT),C-reactive protein(CRP)]at fever onset was assessed using receiver operating characteristic curve analysis.RESULTS Of 80 cases(mean age 42.9±16.5 years;80% male),42.5% had infectious causes,38.7% non-infectious,and 18.8% remained undiagnosed.Pneumonia(26.2%)and bloodstream infections(11.2%)were the most common infectious etiologies,while central fever and thrombophlebitis(each 7.5%)were predominant among non-infectious causes.Sepsis tools showed poor diagnostic accuracy,with area under the receiver operating characteristic curve(AUC)values close to 0.5.PCT demonstrated modest performance(AUC=0.61;optimal cut-off:0.85μg/L),while CRP was paradoxically higher in non-infectious cases(AUC=0.45).Overall mortality was 20% and was highest among undiagnosed patients(33.3%).Fever duration and hospitalization length were significantly greater in infectious cases.CONCLUSION Sepsis tools,PCT,and CRP have limited utility in identifying infectious causes of nFUO in critically ill adults and should not solely guide initial decision-making.
文摘Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.
文摘During infections,nucleic acids of pathogens are also engaged in recognition via several exogenous and cytosolic pattern recognition receptors,such as the toll-like receptors,retinoic acid inducible gene-I-like receptors,and nucleotide-binding and oligomerization domain-like receptors.The binding of the pathogen-derived nucleic acids to their corresponding sensors initiates certain downstream signaling cascades culminating in the release of type-I interferons(IFNs),especially IFN-αand other cytokines to induce proinflammatory responses towards invading pathogens leading to their clearance from the host.Although these sensors are hardwired to recognize pathogen associated molecular patterns,like viral and bacterial nucleic acids,under unusual physiological conditions,such as excessive cellular stress and increased apoptosis,endogenous self-nucleic acids like DNA,RNA,and mitochondrial DNA are also released.The presence of these self-nucleic acids in extranuclear compartments or extracellular spaces or their association with certain proteins sometimes leads to the failure of discriminating mechanisms of nucleic acid sensors leading to proinflammatory responses as seen in autoimmune disorders,like systemic lupus erythematosus,psoriasis and to some extent in type 1 diabetes(T1D).This review discusses the involvement of various nucleic acid sensors in autoimmunity and discusses how aberrant recognition of self-nucleic acids by their sensors activates the innate immune responses during the pathogenesis of T1D.
文摘Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D.Over the past decade and a half,a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease.While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism,a few reports suggest a lack of such association.Pancreatic fat has also been linked with genetic risk of developing T2D,prediabetes,reduced insulin secretion,and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome.With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function,our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved.This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.
文摘Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.
文摘Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping countries.Methods: A total of 312 first degree relativesbelonging to 80 families of children with TD (group 1)and 40 families of age-matched normal children (group2) were screened by thyroid ultrasonography, serum totalthyroxine (T4) and thyroid stimulating hormone (TSH).Results: Thyroid scintigraphy revealed agenesis in78.7% of the patients, ectopic gland in 15%, and hypoplasiain 6.2%. The mean thyroid volumes were similar in parentsand siblings of both groups. Eight (10.6%) mothers in group1 were identified to have thyroid hypoplasia as comparedwith none in group 2 (P=0.03). Serum TSH was signifi cantlyhigher in group 1 than in group 2 (P=0.004). Sixteen (7.8%)subjects (6 mothers, 5 fathers, and 5 siblings) in group 1were found to have subclinical hypothyroidism as comparedto none in group 2 (P<0.05). Four families were identifiedto have thyroid developmental anomalies and abnormalthyroid functions accounting for 5% of cases of familial TDin our cohort.Conclusions: Thyroid developmental anomalies andthyroid function abnormalities are more frequent in firstdegree relatives of children with TD as compared with acontrol population. These findings suggest that possiblythere is a genetic component of TD in Indian patients.
