BACKGROUND:Maxillofacial trauma represents a significant challenge in emergency medicine,requiring both diagnostic accuracy and prompt intervention while balancing immediate life-saving interventions with preservation...BACKGROUND:Maxillofacial trauma represents a significant challenge in emergency medicine,requiring both diagnostic accuracy and prompt intervention while balancing immediate life-saving interventions with preservation of function and aesthetics.The complex anatomy of this region,with its proximity to critical structures,demands a thorough understanding of assessment and management principles.This narrative review aims to provide evidence-based guidelines for emergency physicians managing maxillofacial trauma,with particular emphasis on early recognition of critical injuries,airway management strategies,and special population considerations.METHODS:A narrative review was conducted via a comprehensive literature search of the PubMed and Scopus databases,which focused on maxillofacial trauma management in emergency settings.Articles were selected based on relevance to clinical practice,methodological quality,and current management guidelines.The review synthesized evidence from multiple study types,including original research,systematic reviews,and clinical practice guidelines,to provide practical guidance for emergency physicians.RESULTS:Initial assessment following Advanced Trauma Life Support(ATLS)principles is crucial,with airway management being a primary concern due to the risk of dynamic obstruction.Critical time-sensitive emergencies include orbital compartment syndrome,trapdoor fractures(in pediatric patients),and facial nerve injuries.Computed tomography(CT)imaging remains the gold standard for diagnosis.Special considerations are required for pediatric patients,who present unique anatomical challenges and injury patterns,and for elderly patients,who often have complex medical comorbidities and increased complication risks.Management strategies range from conservative treatment to urgent surgical intervention,with decisions based on the injury pattern and associated complications.CONCLUSION:Emergency physicians must maintain a structured yet fl exible approach to maxillofacial trauma,focusing on early recognition of critical injuries,appropriate airway management,and timely specialist consultation.Understanding injury patterns and their potential complications allows for eff ective risk stratifi cation and treatment planning,ultimately improving patient outcomes.展开更多
In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research sch...In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.展开更多
Background Percutaneous coronary intervention(PCI)is a widely utilized revascularization technique for coronary artery disease(CAD).While clinical and biomarker-based prognostic tools are standard for predicting outco...Background Percutaneous coronary intervention(PCI)is a widely utilized revascularization technique for coronary artery disease(CAD).While clinical and biomarker-based prognostic tools are standard for predicting outcomes,there is growing interest in sarcopenia as a marker of frailty and its potential role in long-term prognosis.The prognostic value of the psoas muscle index(PMI),a sarcopenia metric,remains underexplored in PCI populations regarding long term survival.Methods This single-center retrospective cohort study evaluated 177 patients undergoing PCI from 2015 to 2019.PMI was calculated from computed tomography(CT)imaging at the L3 vertebral level using the formula:(left psoas area+right psoas area)/height2 and expressed in cm^(2)/m^(2).Sarcopenia was defined as the lowest sex-specific PMI quartile.Primary outcomes included 5-year all-cause mortality and 3-point major adverse cardiovascular events(MACE:non-fatal myocardial infarction,ischemic stroke,and cardiac death).Binary linear regression and Cox proportional hazards models were utilized to determine associations between PMI and outcomes Results Sarcopenic patients exhibited significantly higher 5-year all-cause mortality compared to non-sarcopenic counterparts(64.4%vs.35.6%,P<0.001),while no significant difference was observed in 3-point MACE incidence(55.6%vs.51.4%,P=0.520).Sarcopenia was independently associated with all-cause mortality on binary logistic regression(OR=3.49;95%CI:1.69–7.19;P=0.0007),but not MACE(OR=1.00;95%CI:0.50–1.98;P=0.99).In a multivariable Cox regression model,sarcopenia was associated with increased hazard of mortality(HR=1.60;95%CI:0.96–2.66;P=0.071),though this did not reach statistical significance.Kaplan-Meier analysis demonstrated significantly reduced survival among sarcopenic patients(χ^(2)=6.13,P=0.0133).Conclusions PMI is a significant independent predictor of 5-year all-cause mortality in PCI patients,underscoring the prognostic importance of assessing skeletal muscle mass in this population.展开更多
Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most...Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.展开更多
BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and h...BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resul...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.展开更多
Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid co...Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in 'one step', EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.展开更多
Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors ...Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.展开更多
A multi-objective evolutionary optimization method (combining genetic algorithms(GAs)and game theory(GT))is presented for high lift multi-airfoil systems in aerospace engineering.Due to large dimension global op-timiz...A multi-objective evolutionary optimization method (combining genetic algorithms(GAs)and game theory(GT))is presented for high lift multi-airfoil systems in aerospace engineering.Due to large dimension global op-timization problems and the increasing importance of low cost distributed parallel environments,it is a natural idea to replace a globar optimization by decentralized local sub-optimizations using GT which introduces the notion of games associated to an optimization problem.The GT/GAs combined optimization method is used for recon-struction and optimization problems by high lift multi-air-foil desing.Numerical results are favorably compared with single global GAs.The method shows teh promising robustness and efficient parallel properties of coupled GAs with different game scenarios for future advanced multi-disciplinary aerospace techmologies.展开更多
An estimated 285 million adults(aged 20-79 years)worldwide were diagnosed to have diabetes mellitus(DM)in 2010,and this number is projected to grow to 439million adults by the year 2030.Orthopaedic surgeons,regardless...An estimated 285 million adults(aged 20-79 years)worldwide were diagnosed to have diabetes mellitus(DM)in 2010,and this number is projected to grow to 439million adults by the year 2030.Orthopaedic surgeons,regardless of their subspecialty interest,will encounter patients with DM during their career since this epidemic involves both developed and emerging countries.Diabetes results in complications affecting multiple organ systems,potentially resulting in adverse outcomes afterorthopaedic surgery.The purpose of this review is to discuss the pathophysiology of DM and its potential for impacting orthopaedic surgery patients.Diabetes adversely affects the outcome of all orthopaedic surgery subspecialties including foot and ankle,upper extremity,adult reconstructive,pediatrics,spine surgery and sports medicine.Poorly controlled diabetes negatively impacts bone,soft tissue,ligament and tendon healing.It is the complications of diabetes such as neuropathy,peripheral artery disease,and end stage renal disease which contributes to adverse outcomes.Well controlled diabetic patients without comorbidities have similar outcomes to patients without diabetes.Orthopaedic surgeons should utilize consultants who will assist in inpatient glycemic management as well as optimizing long term glycemic control.展开更多
文摘BACKGROUND:Maxillofacial trauma represents a significant challenge in emergency medicine,requiring both diagnostic accuracy and prompt intervention while balancing immediate life-saving interventions with preservation of function and aesthetics.The complex anatomy of this region,with its proximity to critical structures,demands a thorough understanding of assessment and management principles.This narrative review aims to provide evidence-based guidelines for emergency physicians managing maxillofacial trauma,with particular emphasis on early recognition of critical injuries,airway management strategies,and special population considerations.METHODS:A narrative review was conducted via a comprehensive literature search of the PubMed and Scopus databases,which focused on maxillofacial trauma management in emergency settings.Articles were selected based on relevance to clinical practice,methodological quality,and current management guidelines.The review synthesized evidence from multiple study types,including original research,systematic reviews,and clinical practice guidelines,to provide practical guidance for emergency physicians.RESULTS:Initial assessment following Advanced Trauma Life Support(ATLS)principles is crucial,with airway management being a primary concern due to the risk of dynamic obstruction.Critical time-sensitive emergencies include orbital compartment syndrome,trapdoor fractures(in pediatric patients),and facial nerve injuries.Computed tomography(CT)imaging remains the gold standard for diagnosis.Special considerations are required for pediatric patients,who present unique anatomical challenges and injury patterns,and for elderly patients,who often have complex medical comorbidities and increased complication risks.Management strategies range from conservative treatment to urgent surgical intervention,with decisions based on the injury pattern and associated complications.CONCLUSION:Emergency physicians must maintain a structured yet fl exible approach to maxillofacial trauma,focusing on early recognition of critical injuries,appropriate airway management,and timely specialist consultation.Understanding injury patterns and their potential complications allows for eff ective risk stratifi cation and treatment planning,ultimately improving patient outcomes.
文摘In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.
文摘Background Percutaneous coronary intervention(PCI)is a widely utilized revascularization technique for coronary artery disease(CAD).While clinical and biomarker-based prognostic tools are standard for predicting outcomes,there is growing interest in sarcopenia as a marker of frailty and its potential role in long-term prognosis.The prognostic value of the psoas muscle index(PMI),a sarcopenia metric,remains underexplored in PCI populations regarding long term survival.Methods This single-center retrospective cohort study evaluated 177 patients undergoing PCI from 2015 to 2019.PMI was calculated from computed tomography(CT)imaging at the L3 vertebral level using the formula:(left psoas area+right psoas area)/height2 and expressed in cm^(2)/m^(2).Sarcopenia was defined as the lowest sex-specific PMI quartile.Primary outcomes included 5-year all-cause mortality and 3-point major adverse cardiovascular events(MACE:non-fatal myocardial infarction,ischemic stroke,and cardiac death).Binary linear regression and Cox proportional hazards models were utilized to determine associations between PMI and outcomes Results Sarcopenic patients exhibited significantly higher 5-year all-cause mortality compared to non-sarcopenic counterparts(64.4%vs.35.6%,P<0.001),while no significant difference was observed in 3-point MACE incidence(55.6%vs.51.4%,P=0.520).Sarcopenia was independently associated with all-cause mortality on binary logistic regression(OR=3.49;95%CI:1.69–7.19;P=0.0007),but not MACE(OR=1.00;95%CI:0.50–1.98;P=0.99).In a multivariable Cox regression model,sarcopenia was associated with increased hazard of mortality(HR=1.60;95%CI:0.96–2.66;P=0.071),though this did not reach statistical significance.Kaplan-Meier analysis demonstrated significantly reduced survival among sarcopenic patients(χ^(2)=6.13,P=0.0133).Conclusions PMI is a significant independent predictor of 5-year all-cause mortality in PCI patients,underscoring the prognostic importance of assessing skeletal muscle mass in this population.
基金supported in part by DOD Idea Development Award(HT9425-23-1-0295)NIH grants(R01 CA265897 and R21 CA280467)by the Department of Urology,University of Pittsburgh School of Medicine,Pittsburgh,PA,USA。
文摘Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
文摘BACKGROUND:BRASH syndrome(Bradycardia,Renal failure,AV nodal blockade,Shock,and Hyperkalemia)is a recently described clinical entity characterized by synergistic interaction between AV nodal blocking medications and hyperkalemia.Despite increasing recognition,its clinical characteristics,risk factors,and outcomes remain poorly defined.The rationale of this review is to provide clinicians an upto-date overview of the most commonly encountered risk factors,triggers,clinical pictures,usual lab values,complications and outcomes,via the systemic analysis of currently published cases.METHODS:A systematic review was conducted using MEDLINE,Web of Science,and Cochrane Library databases through December 2024.Case reports,case series,and conference abstracts involving adult patients with BRASH syndrome were included.Data extraction focused on demographics,clinical presentations,laboratory findings,management strategies,and outcomes.RESULTS:Analysis included 131 patients from 111 published cases.Mean age was(71±13)years,with female predominance(58.1%).Hypertension(77.0%),chronic kidney disease(48.4%),and diabetes mellitus(46.7%)were the most common comorbidities.Beta-blockers were the predominant medication(76.5%).Most common presenting symptoms were syncope(17.9%),generalized weakness(16.2%),and altered mental status(11.9%).Mean potassium level was 6.6 mEq/L,with more than half of cases presenting with non-severe hyperkalemia(<6.5 mEq/L).Management often required multimodal therapy,with 50.8% of patients requiring vasopressors and 31.6% requiring hemodialysis.CONCLUSION:This systematic review provides the most comprehensive analysis of BRASH syndrome to date,demonstrating that while potentially serious,outcomes are generally favorable with appropriate recognition and management.The syndrome can develop even with modest hyperkalemia,particularly in elderly patients with multiple comorbidities.Early recognition and systematic management addressing all components of the syndrome appear crucial for optimal outcomes.
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
文摘Pancreatic fluid collections (PFCs) develop secondary to either fluid leakage or liquefaction of pancreatic necrosis following acute pancreatitis, chronic pancreatitis, surgery or abdominal trauma. Pancreatic fluid collections include acute fluid collections, acute and chronic pancreatic pseudocysts, pancreatic abscesses and pancreatic necrosis. Before the introduction of linear endoscopic ultrasound (EUS) in the 1990s and the subsequent development of endoscopic ultrasound-guided drainage (EUS-GD) procedures, the available options for drainage in symptomatic PFCs included surgical drainage, percutaneous drainage using radiological guidance and conventional endoscopic transmural drainage. In recent years, it has gradually been recog-nized that, due to its lower morbidity rate compared to the surgical and percutaneous approaches, endoscopic treatment may be the preferred first-line approach for managing symptomatic PFCs. Endoscopic ultrasound-guided drainage has the following advantages, when compared to other alternatives such as surgical, per-cutaneous and non-EUS-guided endoscopic drainage.EUS-GD is less invasive than surgery and therefore does not require general anesthesia. The morbidity rate is lower, recovery is faster and the costs are lower. EUS-GD can avoid local complications related to per-cutaneous drainage. Because the endoscope is placed adjacent to the fluid collection, it can have direct ac-cess to the fluid cavity, unlike percutaneous drainage which traverses the abdominal wall. Complications such as bleeding, inadvertent puncture of adjacent viscera, secondary infection and prolonged periods of drainage with resultant pancreatico-cutaneous fistulae may be avoided. The only difference between EUS and non-EUS drainage is the initial step, namely, gaining access to the pancreatic fluid collection. All the sub-sequent steps are similar, i.e., insertion of guide-wires with fluoroscopic guidance, balloon dilatation of the cystogastrostomy and insertion of transmural stents or nasocystic catheters. With the introduction of the EUS-scope equipped with a large operative channel which permits drainage of the PFCs in 'one step', EUS-GD has been increasingly carried out in many tertiary care centers and has expanded the safety and efficacy of this modality, allowing access to and drainage of overly challenging fluid collections. However, the nature of the PFCs determines the outcome of this procedure. The technique and review of current literature regarding EUS-GD of PFCs will be discussed.
文摘Cervical cancer is the third most common cancer in women worldwide; definitive radiation therapy and concurrent chemotherapy is the accepted standard of care for patients with node positive or locally advanced tumors > 4 cm. Brachytherapy is an important part of definitive radiotherapy shown to improve overall survival. While results for two-dimensional X-ray based brachytherapy have been good in terms of local control especially for early stage disease, unexplained toxicities and treatment failures remain. Improvements in brachytherapy planning have more recently paved the way for three-dimensional image-based brachytherapy with volumetric optimization which increases tumor control, reduces toxicity, and helps predict outcomes.Advantages of image-based brachytherapy include:improved tumor coverage(especially for large volume disease), decreased dose to critical organs(especially for small cervix), confirmation of applicator placement, and accounting for sigmoid colon dose. A number of modalities for image-based brachytherapy have emerged including: magnetic resonance imaging(MRI),computed tomography(CT), CT-MRI hybrid, and ultrasound with respective benefits and outcomes data. Forpractical application of image-based brachytherapy the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology Working Group and American Brachytherapy Society working group guideline serve as invaluable tools, additionally here-in we outline our institutional clinical integration of these guidelines. While the body of literature supporting image-based brachytherapy continues to evolve a number of uncertainties and challenges remain including: applicator reconstruction, increasing resource/cost demands, mobile four-dimensional targets and organs-at-risk, and accurate contouring of "grey zones" to avoid marginal miss. Ongoing studies, including the prospective EMBRACE(an international study of MRI-guided brachytherapy in locally advanced cervical cancer) trial, along with continued improvements in imaging, contouring, quality assurance, physics, and brachytherapy delivery promise to perpetuate the advancement of image-based brachytherapy to optimize outcomes for cervical cancer patients.
文摘A multi-objective evolutionary optimization method (combining genetic algorithms(GAs)and game theory(GT))is presented for high lift multi-airfoil systems in aerospace engineering.Due to large dimension global op-timization problems and the increasing importance of low cost distributed parallel environments,it is a natural idea to replace a globar optimization by decentralized local sub-optimizations using GT which introduces the notion of games associated to an optimization problem.The GT/GAs combined optimization method is used for recon-struction and optimization problems by high lift multi-air-foil desing.Numerical results are favorably compared with single global GAs.The method shows teh promising robustness and efficient parallel properties of coupled GAs with different game scenarios for future advanced multi-disciplinary aerospace techmologies.
文摘An estimated 285 million adults(aged 20-79 years)worldwide were diagnosed to have diabetes mellitus(DM)in 2010,and this number is projected to grow to 439million adults by the year 2030.Orthopaedic surgeons,regardless of their subspecialty interest,will encounter patients with DM during their career since this epidemic involves both developed and emerging countries.Diabetes results in complications affecting multiple organ systems,potentially resulting in adverse outcomes afterorthopaedic surgery.The purpose of this review is to discuss the pathophysiology of DM and its potential for impacting orthopaedic surgery patients.Diabetes adversely affects the outcome of all orthopaedic surgery subspecialties including foot and ankle,upper extremity,adult reconstructive,pediatrics,spine surgery and sports medicine.Poorly controlled diabetes negatively impacts bone,soft tissue,ligament and tendon healing.It is the complications of diabetes such as neuropathy,peripheral artery disease,and end stage renal disease which contributes to adverse outcomes.Well controlled diabetic patients without comorbidities have similar outcomes to patients without diabetes.Orthopaedic surgeons should utilize consultants who will assist in inpatient glycemic management as well as optimizing long term glycemic control.
