AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three s...AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on- HRCT-were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular(CLE), paraseptal(PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia(UIP), probable UIP and nonspecific interstitial pneumonia(NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis(Coarseness), extent of emphysema(emphysema), extent of interstitial lung disease(Tot Ext ILD), extent of reticular pattern not otherwise specified(Ret NOS), extent of ground glass opacity with traction bronchiectasis(extG GOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity(DLCO) and systolic pulmonary arterial pressure were compared among the groups.RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema(P < 0.001) and a lower extent of interstitial lung disease(P < 0.002), reticular pattern not otherwise specified(P < 0.023), extent of ground glass opacity with traction bronchiectasis(P < 0.002), extent of honeycombing(P < 0.001) and coarseness of fibrosis(P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema(P < 0.05), total lung capacity(P < 0.01) and diffusion capacity(DLCO)(P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, extent of honeycombing and coarseness of fibrosis(0.039 > P > 0.000). Although the pulmonary arterial pressure was higher in typical UIP group relative to the NSIP group, the difference was not statistically significant.CONCLUSION: In CPFE patients, paraseptal emphysema is associated more with UIP-HRCT pattern and higher extent of fibrosis than centrilobular emphysema.展开更多
Prediction of weaning success from invasive mechanical ventilation remains a challenge in everyday clinical practice.Several prediction scores have been developed to guide success during spontaneous breathing trials t...Prediction of weaning success from invasive mechanical ventilation remains a challenge in everyday clinical practice.Several prediction scores have been developed to guide success during spontaneous breathing trials to help with weaning decisions.These scores aim to provide a structured framework to support clinical judgment.However,their effectiveness varies across patient populations,and their predictive accuracy remains inconsistent.In this review,we aim to identify the strengths and limitations of commonly used clinical prediction tools in assessing readiness for ventilator liberation.While scores such as the Rapid Shallow Breathing Index and the Integrative Weaning Index are widely adopted,their sensitivity and specificity often fall short in complex clinical settings.Factors such as underlying disease pathophysiology,patient characteristics,and clinician subjectivity impact score performance and reliability.Moreover,disparities in validation across diverse populations limit generalizability.With growing interest in artificial intelligence(AI)and machine learning,there is potential for enhanced prediction models that integrate multidimensional data and adapt to individual patient profiles.However,current AI approaches face challenges related to interpretability,bias,and ethical implementation.This paper underscores the need for more robust,individualized,and transparent prediction systems and advocates for careful integration of emerging technologies into clinical workflows to optimize weaning success and patient outcomes.展开更多
Obstructive sleep apnea(OSA)is frequently associated with obesity and metabolic syndrome.Also frequently associated with metabolic syndrome is type 2 diabetes mellitus(T2DM).Therefore,it is common to find OSA and T2DM...Obstructive sleep apnea(OSA)is frequently associated with obesity and metabolic syndrome.Also frequently associated with metabolic syndrome is type 2 diabetes mellitus(T2DM).Therefore,it is common to find OSA and T2DM together in individuals with metabolic syndrome.Additionally,both OSA and T2DM have a common pathophysiological link with development of insulin resistance.Individuals with severe insulin resistance are likely to have inadequate glycemic control.Long standing poorly controlled T2DM is associated with debilitating microvascular complications such as retinopathy,nephropathy,neuropathy and macrovascular complications such as coronary artery and cerebrovascular disease.There is extensively published literature exploring the cause-effect relationship between OSA and T2DM.In this article we provide an in-depth review of the complex pathophysiological mechanisms linking OSA to T2DM.Specifically,this review focusses on the effect of OSA on the microvascular complications of T2DM such as retinopathy,nephropathy and neuropathy.Additionally,we review the current literature on the effect of continuous positive airway pressure use in individuals with T2DM and OSA.展开更多
The role of Toll-like receptors(TLRs)in pathogen recognition has been expeditiously advanced in recent years.However,investigations into the function of TLRs in non-infectious tissue injury have just begun.Previously,...The role of Toll-like receptors(TLRs)in pathogen recognition has been expeditiously advanced in recent years.However,investigations into the function of TLRs in non-infectious tissue injury have just begun.Previously,we and others have demonstrated that fragmented hyaluronan(HA)accumulates during tissue injury.CD44 is required to clear HA during tissue injury,and impaired clearance of HA results in unremitting inflammation.Additionally,fragmented HA stimulates the expression of inflammatory genes by inflammatory cells at the injury site.Recently,we identified that HA fragments require both TLR2 and TLR4 to stimulate mouse macrophages to produce inflammatory chemokines and cytokines.In a non-infectious lung injury model,mice deficient in both TLR2 and TLR4 show an impaired transepithelial migration of inflammatory cells,increased tissue injury,elevated lung epithelial cell apoptosis,and decreased survival.Lung epithelial cell overexpression of high molecular mass HA protected mice against acute lung injury and apoptosis,in part through TLR-dependent basal activation of NF-κB.The exaggerated injury in TLR2 and TLR4 deficient mice appears to be due to impaired HA-TLR interactions on epithelial cells.These studies identify that host matrix component HA and TLR interactions provide signals that initiate inflammatory responses,maintain epithelial cell integrity,and promote recovery from acute lung injury.展开更多
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancrea...Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.展开更多
Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review ex...Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severelyill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis.展开更多
Diabetes mellitus(DM) is a highly prevalent condition affecting about 347 million people worldwide. In addition to its numerous clinical implications, DM also exerts a negative effect on patient's sleep quality.Im...Diabetes mellitus(DM) is a highly prevalent condition affecting about 347 million people worldwide. In addition to its numerous clinical implications, DM also exerts a negative effect on patient's sleep quality.Impaired sleep quality disrupts the adequate glycemic control regarded as corner stone in DM management and also lead to many deleterious effects causing a profound impact on health related quality of life. This article outlines various factors leading to impaired sleep quality among diabetics and delineates how individual factor influences sleep. The article also discusses potential interventions and lifestyle changes to promote healthy sleep among diabetics.展开更多
Background and Objectives:Lung cancer is the most common cancer and cancer related cause of death worldwide.However,the association between sleep duration and incident lung cancer has not been investigated in a prospe...Background and Objectives:Lung cancer is the most common cancer and cancer related cause of death worldwide.However,the association between sleep duration and incident lung cancer has not been investigated in a prospective cohort study.Methods:We prospectively examined the association between sleep duration and incident lung cancer in a cohort of 21,026 United States(US)male physicians.Self-reported sleep duration was ascertained during 2002 annual follow-up questionnaire.Incident lung cancer was ascertained through yearly follow-up questionnaires.Cox regression was used to estimate relative risk of incident lung cancer.Results:The average age at baseline was 68.3±8.8 yr.During a mean follow up of 7.5(±2.2)yr,150 cases of lung cancer occurred.Using 7 h of sleep as the reference group,multivariable adjusted hazard ratios(95%CI)for lung cancer were 1.18(0.77-1.82),1.0(ref),and 0.97(0.67-1.41)from lowest to the highest category of sleep duration(P for quadratic trend 0.697),respectively.In a secondary analysis,smoking status did not modify the sleep duration-lung cancer association(P=0.78).There was no evidence for an interaction between sleep duration and sleep apnea on the risk of lung cancer either(P=0.65).Conclusions:Our data failed to show a higher risk of lung cancer in association with altered sleep duration among US male physicians.展开更多
Background: Computed tomography (CT) and bronchoscopy have been shown to improve the detection rates of peripheral and central lung cancers (LC), respectively. However, the performance of the combination of CT and bro...Background: Computed tomography (CT) and bronchoscopy have been shown to improve the detection rates of peripheral and central lung cancers (LC), respectively. However, the performance of the combination of CT and bronchoscopy in detecting LC, in high-risk patients, is not clear. Patients & Methods: This prospective study included 205 high-risk patients with a history of at least 2 of the following risk factors: (1) heavy smoking;(2) aero-digestive cancer;(3) pulmonary asbestosis or;(4) chronic obstructive pulmonary disease. Patients were offered chest X-ray, sputum cytology, conventional white-light followed by autofluorescence beonchoscopy (WL/AFB) and low-dose spiral CT both at baseline and follow-up visits. Results: Seven patients (3.4%) were diagnosed with LC or carcinoma in-situ (CIS) at baseline: CT evaluation detected 5 LC/CIS, while WL/AFB evaluation also identified 5 LC/CIS, 2 of which were not detected on CT. Six (85%) of these baseline lesions were early stage (0/IA). The relative-sensitivity of CT with WL/ AFB was 40% better than CT alone. On four year follow-up, 20 patients (9.8%) were diagnosed with an LC/CIS. CT with WL/AFB detected 19 cases (95%), whereas CT alone detected 15 cases (75%). Conclusion: Bimodality surveillance with spiral CT and WL/AFB can improve the detection of early stage LCs among high-risk展开更多
AIMTo determine the impact of transjugular intrahepatic porto-systemic shunt (TIPS) on post liver transplantation (LT) outcomes. METHODSUtilizing the United Network for Organ Sharing (UNOS) database, we compared patie...AIMTo determine the impact of transjugular intrahepatic porto-systemic shunt (TIPS) on post liver transplantation (LT) outcomes. METHODSUtilizing the United Network for Organ Sharing (UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay (LOS), and need for re-LT were studied. For evaluation of mean differences between baseline characteristics for patients with and without TIPS, we used unpaired t-tests for continuous measures and χ<sup>2</sup> tests for categorical measures. We estimated the impact of TIPS on each of the outcome measures. Multivariate analyses were conducted on the study population to explore the effect of TIPS on 30-d mortality post-LT, need for re-LT and LOS. All covariates were included in logistic regression analysis. RESULTSWe included adult patients (age ≥ 18 years) who underwent LT from May 2002 to September 2013. Only those undergoing TIPS after listing and before liver transplant were included in the TIPS group. We excluded patients with variceal bleeding within two weeks of listing for LT and those listed for acute liver failure or hepatocellular carcinoma. Of 114770 LT in the UNOS database, 32783 (28.5%) met inclusion criteria. Of these 1366 (4.2%) had TIPS between the time of listing and LT. We found that TIPS increased the days on waitlist (408 ± 553 d) as compared to those without TIPS (183 ± 330 d), P P P = 0.001) by TIPS to LOS. CONCLUSIONTIPS did increase time on waitlist for LT. More importantly, TIPS was not associated with 30-d mortality and re-LT, but it did lengthen hospital LOS after transplantation.展开更多
AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ...AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.展开更多
Systemic sclerosis (scleroderma) is a connective tissue disease characterized by vascular dysfunction and fibrosis that can affect multiple organ systems. We present case of primary cardiac involvement and the diagnos...Systemic sclerosis (scleroderma) is a connective tissue disease characterized by vascular dysfunction and fibrosis that can affect multiple organ systems. We present case of primary cardiac involvement and the diagnostic role of cardiac MRI. Cardiovascular magnetic resonance imaging (MRI) is an accurate, quantitative method for the non-invasive assessment of myocardial perfusion. The presence of clinically apparent myocardial involvement in scleroderma portends a very poor prognosis. One study of US veterans found that clinical cardiac disease in scleroderma was associated with a 70% mortality rate at five years. Management of heart failure and conduction system abnormalities in scleroderma is similar to other cardiac disease. It includes afterload reduction, beta-blockade, defibrillator placement, etc. Patients with reduced cardiac function and normal coronary arteries may benefit from increased immune suppresion.展开更多
Non-typhoidal salmonellosis has emerged as an invasive infection in industrialized countries. Bacteremia and pleuropulmonary involvement usually occur in the setting of chronic illnesses such as diabetes, malignancies...Non-typhoidal salmonellosis has emerged as an invasive infection in industrialized countries. Bacteremia and pleuropulmonary involvement usually occur in the setting of chronic illnesses such as diabetes, malignancies and HIV. We present three cases of non-typhoidal salmonellosis in immunocompetent patients presenting over a year period. A 66-year-old female presented with septic shock. She was started on vancomycin, doripenem and ciprofloxacin. Her blood cultures grew Salmonella enteridis that was also isolated from her urine and bronchoalveolar lavage fluid. Stool cultures were negative for Salmonella species. She had no epidemiologic risk factors for invasive Salmonella infection. Her immunodeficiency workup was negative. CT scan abdomen was unremarkable. She became hemodynamically stable and completed a two week course of Ceftriaxone without complications. A 58-year-old female presented with sub-acute onset of fever and dyspnea. CT chest showed bilateral pleural effusions. Left sided thoracentesis revealed purulent fluid consistent with empyema. Pleural fluid cultures grew Salmonella Group D. Blood, sputum and stool cultures remained negative. She denied consumption of raw eggs or exposure to pets, farm animals or reptiles. She was treated with Ceftriaxone for two weeks along with pigtail catheter drainage. Her immunodeficiency workup was negative. A 62-year-old man presented with acute left lower quadrant abdominal pain. CT Abdomen revealed a focal abnormality in abdominal aorta consistent with mycotic aneurysm. Blood cultures grew Salmonella Group D resistant to cephalosporins and bactrim, hence treatment with Meropenem was started. Subsequent blood, respiratory tract, urine and stool cultures remained negative. Due to high risk of perioperative complications, it was decided to follow the mycotic aneurysm expectantly. Antibiotics were deescalated to six weeks of Ertapenem followed by long term quinolone prophylaxis. He also did not have any epidemiologic risk factors for salmonellosis and his immunodeficiency workup was negative. These cases highlight the pathogenesis of this invasive organism that is transmitted though food borne route and causes bacteremic seeding of various sites such as lungs and pleura. It is extremely important to consider this organism in patients presenting with gram negative bacteremia leading to septic shock as well as endovascular infections.展开更多
Background: Chronic obstructive pulmonary disease (COPD) and presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on th...Background: Chronic obstructive pulmonary disease (COPD) and presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with endobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25 (11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Regression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age, gender and tobacco smoking. Results: Patients with FEV1% of <50% had 4.5 times greater risk of being diagnosed with an EPL [95% confidence interval: 1.93-10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥80. COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p = 0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among patients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with EPL who need more intense LC surveillance.展开更多
Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring sy...Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma,few studies have focused on prediction accuracy and application in patients with traumatic brain injury.The shock index(SI)which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI.In this editorial we comment on a publication by Carteri et al wherein they perform a retrospective analysis studying the predictive potential of SI and its variants in populations with severe traumatic brain injury.展开更多
Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP...Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP)is generally considered an acute time-limited illness,it is associated with high long-term mortality,with nearly one-third of patients requiring hospitalization dying within one year.An increasing trend of detecting multidrug-resistant(MDR)organisms causing CAP has been observed,especially in the Western world.In this editorial,we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia,bacteremia,and infective endocarditis that led to the patient’s death.The early detection of these resistant organisms helps improve patient outcomes.Significant advances have been made in the biotechnological and research space,but preventive measures,diagnostic techniques,and treatment strategies need to be developed.展开更多
Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep...Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.展开更多
Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most common diseases encountered by the worldwide population, with high social and economic burdens. Significant emphasis has been placed on o...Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most common diseases encountered by the worldwide population, with high social and economic burdens. Significant emphasis has been placed on obtaining blood pressure, body mass index, and placing importance on screening for signs and symptoms pointing towards cardiovascular disease. Symptoms related to sleep, or screening for sleep apnea has been overlooked by cardiac, diabetic, pulmonary and general medicine clinics despite recommendations for screening by several societies. In recent years, there is mounting data where obesity and obstructive sleep apnea sit at the epicenter and its control can lead to improvement and prevention of diabetes and cardiovascular complications. This editorial raises questions as to why obstructive sleep apnea screening should be included as yet another vital sign during patient initial inpatient or outpatient visit.展开更多
Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global...Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global sodium consumption greatly exceeds guidelines recommended by all medical institutions. This review synthesizes the data of landmark mammalian and human studies which investigated the role of sodium in the pathogenesis of hypertension, along with modern studies questioning this relationship. Recent studies concerning the potential pathways by which high-sodium concentration induces hypertension were reviewed. Human trials and population studies revealed a strong correlation between high blood pressure and average dietary sodium; and animal studies found a dramatic reduction in vascular function in a variety of mammals treated with high-sodium diets. In spite of a few contrarian studies, we found overwhelming evidence that elevated sodium consumption could cause hypertension展开更多
文摘AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography(HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema(CPFE).METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on- HRCT-were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular(CLE), paraseptal(PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia(UIP), probable UIP and nonspecific interstitial pneumonia(NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis(Coarseness), extent of emphysema(emphysema), extent of interstitial lung disease(Tot Ext ILD), extent of reticular pattern not otherwise specified(Ret NOS), extent of ground glass opacity with traction bronchiectasis(extG GOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity(DLCO) and systolic pulmonary arterial pressure were compared among the groups.RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema(P < 0.001) and a lower extent of interstitial lung disease(P < 0.002), reticular pattern not otherwise specified(P < 0.023), extent of ground glass opacity with traction bronchiectasis(P < 0.002), extent of honeycombing(P < 0.001) and coarseness of fibrosis(P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema(P < 0.05), total lung capacity(P < 0.01) and diffusion capacity(DLCO)(P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise specified, extent of ground glass opacity with traction bronchiectasis, extent of honeycombing and coarseness of fibrosis(0.039 > P > 0.000). Although the pulmonary arterial pressure was higher in typical UIP group relative to the NSIP group, the difference was not statistically significant.CONCLUSION: In CPFE patients, paraseptal emphysema is associated more with UIP-HRCT pattern and higher extent of fibrosis than centrilobular emphysema.
文摘Prediction of weaning success from invasive mechanical ventilation remains a challenge in everyday clinical practice.Several prediction scores have been developed to guide success during spontaneous breathing trials to help with weaning decisions.These scores aim to provide a structured framework to support clinical judgment.However,their effectiveness varies across patient populations,and their predictive accuracy remains inconsistent.In this review,we aim to identify the strengths and limitations of commonly used clinical prediction tools in assessing readiness for ventilator liberation.While scores such as the Rapid Shallow Breathing Index and the Integrative Weaning Index are widely adopted,their sensitivity and specificity often fall short in complex clinical settings.Factors such as underlying disease pathophysiology,patient characteristics,and clinician subjectivity impact score performance and reliability.Moreover,disparities in validation across diverse populations limit generalizability.With growing interest in artificial intelligence(AI)and machine learning,there is potential for enhanced prediction models that integrate multidimensional data and adapt to individual patient profiles.However,current AI approaches face challenges related to interpretability,bias,and ethical implementation.This paper underscores the need for more robust,individualized,and transparent prediction systems and advocates for careful integration of emerging technologies into clinical workflows to optimize weaning success and patient outcomes.
文摘Obstructive sleep apnea(OSA)is frequently associated with obesity and metabolic syndrome.Also frequently associated with metabolic syndrome is type 2 diabetes mellitus(T2DM).Therefore,it is common to find OSA and T2DM together in individuals with metabolic syndrome.Additionally,both OSA and T2DM have a common pathophysiological link with development of insulin resistance.Individuals with severe insulin resistance are likely to have inadequate glycemic control.Long standing poorly controlled T2DM is associated with debilitating microvascular complications such as retinopathy,nephropathy,neuropathy and macrovascular complications such as coronary artery and cerebrovascular disease.There is extensively published literature exploring the cause-effect relationship between OSA and T2DM.In this article we provide an in-depth review of the complex pathophysiological mechanisms linking OSA to T2DM.Specifically,this review focusses on the effect of OSA on the microvascular complications of T2DM such as retinopathy,nephropathy and neuropathy.Additionally,we review the current literature on the effect of continuous positive airway pressure use in individuals with T2DM and OSA.
基金supposed by US National Institutes of Health Grants HL57486 and A152487.
文摘The role of Toll-like receptors(TLRs)in pathogen recognition has been expeditiously advanced in recent years.However,investigations into the function of TLRs in non-infectious tissue injury have just begun.Previously,we and others have demonstrated that fragmented hyaluronan(HA)accumulates during tissue injury.CD44 is required to clear HA during tissue injury,and impaired clearance of HA results in unremitting inflammation.Additionally,fragmented HA stimulates the expression of inflammatory genes by inflammatory cells at the injury site.Recently,we identified that HA fragments require both TLR2 and TLR4 to stimulate mouse macrophages to produce inflammatory chemokines and cytokines.In a non-infectious lung injury model,mice deficient in both TLR2 and TLR4 show an impaired transepithelial migration of inflammatory cells,increased tissue injury,elevated lung epithelial cell apoptosis,and decreased survival.Lung epithelial cell overexpression of high molecular mass HA protected mice against acute lung injury and apoptosis,in part through TLR-dependent basal activation of NF-κB.The exaggerated injury in TLR2 and TLR4 deficient mice appears to be due to impaired HA-TLR interactions on epithelial cells.These studies identify that host matrix component HA and TLR interactions provide signals that initiate inflammatory responses,maintain epithelial cell integrity,and promote recovery from acute lung injury.
基金Supported by National Institutes of Health,Nos.R01 DK067255 and R01 AI080581
文摘Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.
文摘Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severelyill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis.
文摘Diabetes mellitus(DM) is a highly prevalent condition affecting about 347 million people worldwide. In addition to its numerous clinical implications, DM also exerts a negative effect on patient's sleep quality.Impaired sleep quality disrupts the adequate glycemic control regarded as corner stone in DM management and also lead to many deleterious effects causing a profound impact on health related quality of life. This article outlines various factors leading to impaired sleep quality among diabetics and delineates how individual factor influences sleep. The article also discusses potential interventions and lifestyle changes to promote healthy sleep among diabetics.
基金supported by grants CA-34944, CA- 40360 and CA- 097193 from the National Cancer Institutegrants HL-26490, and H L -34595, from the National Heart, Lung and Blood Institute of Health
文摘Background and Objectives:Lung cancer is the most common cancer and cancer related cause of death worldwide.However,the association between sleep duration and incident lung cancer has not been investigated in a prospective cohort study.Methods:We prospectively examined the association between sleep duration and incident lung cancer in a cohort of 21,026 United States(US)male physicians.Self-reported sleep duration was ascertained during 2002 annual follow-up questionnaire.Incident lung cancer was ascertained through yearly follow-up questionnaires.Cox regression was used to estimate relative risk of incident lung cancer.Results:The average age at baseline was 68.3±8.8 yr.During a mean follow up of 7.5(±2.2)yr,150 cases of lung cancer occurred.Using 7 h of sleep as the reference group,multivariable adjusted hazard ratios(95%CI)for lung cancer were 1.18(0.77-1.82),1.0(ref),and 0.97(0.67-1.41)from lowest to the highest category of sleep duration(P for quadratic trend 0.697),respectively.In a secondary analysis,smoking status did not modify the sleep duration-lung cancer association(P=0.78).There was no evidence for an interaction between sleep duration and sleep apnea on the risk of lung cancer either(P=0.65).Conclusions:Our data failed to show a higher risk of lung cancer in association with altered sleep duration among US male physicians.
文摘Background: Computed tomography (CT) and bronchoscopy have been shown to improve the detection rates of peripheral and central lung cancers (LC), respectively. However, the performance of the combination of CT and bronchoscopy in detecting LC, in high-risk patients, is not clear. Patients & Methods: This prospective study included 205 high-risk patients with a history of at least 2 of the following risk factors: (1) heavy smoking;(2) aero-digestive cancer;(3) pulmonary asbestosis or;(4) chronic obstructive pulmonary disease. Patients were offered chest X-ray, sputum cytology, conventional white-light followed by autofluorescence beonchoscopy (WL/AFB) and low-dose spiral CT both at baseline and follow-up visits. Results: Seven patients (3.4%) were diagnosed with LC or carcinoma in-situ (CIS) at baseline: CT evaluation detected 5 LC/CIS, while WL/AFB evaluation also identified 5 LC/CIS, 2 of which were not detected on CT. Six (85%) of these baseline lesions were early stage (0/IA). The relative-sensitivity of CT with WL/ AFB was 40% better than CT alone. On four year follow-up, 20 patients (9.8%) were diagnosed with an LC/CIS. CT with WL/AFB detected 19 cases (95%), whereas CT alone detected 15 cases (75%). Conclusion: Bimodality surveillance with spiral CT and WL/AFB can improve the detection of early stage LCs among high-risk
文摘AIMTo determine the impact of transjugular intrahepatic porto-systemic shunt (TIPS) on post liver transplantation (LT) outcomes. METHODSUtilizing the United Network for Organ Sharing (UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay (LOS), and need for re-LT were studied. For evaluation of mean differences between baseline characteristics for patients with and without TIPS, we used unpaired t-tests for continuous measures and χ<sup>2</sup> tests for categorical measures. We estimated the impact of TIPS on each of the outcome measures. Multivariate analyses were conducted on the study population to explore the effect of TIPS on 30-d mortality post-LT, need for re-LT and LOS. All covariates were included in logistic regression analysis. RESULTSWe included adult patients (age ≥ 18 years) who underwent LT from May 2002 to September 2013. Only those undergoing TIPS after listing and before liver transplant were included in the TIPS group. We excluded patients with variceal bleeding within two weeks of listing for LT and those listed for acute liver failure or hepatocellular carcinoma. Of 114770 LT in the UNOS database, 32783 (28.5%) met inclusion criteria. Of these 1366 (4.2%) had TIPS between the time of listing and LT. We found that TIPS increased the days on waitlist (408 ± 553 d) as compared to those without TIPS (183 ± 330 d), P P P = 0.001) by TIPS to LOS. CONCLUSIONTIPS did increase time on waitlist for LT. More importantly, TIPS was not associated with 30-d mortality and re-LT, but it did lengthen hospital LOS after transplantation.
文摘AIM To examine the effect of center size on survival differences between simultaneous liver kidney transplantation(SLKT) and liver transplantation alone(LTA) in SLKT-listed patients.METHODS The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Posttransplant survival was evaluated using stratified Cox regression with interaction between transplant type(LTA vs SLKT) and center volume.RESULTS During the study period, 393 of 4580 patients(9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients(180/393, 46%) than SLKT recipients(1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio(HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction(HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed.CONCLUSION In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes.
文摘Systemic sclerosis (scleroderma) is a connective tissue disease characterized by vascular dysfunction and fibrosis that can affect multiple organ systems. We present case of primary cardiac involvement and the diagnostic role of cardiac MRI. Cardiovascular magnetic resonance imaging (MRI) is an accurate, quantitative method for the non-invasive assessment of myocardial perfusion. The presence of clinically apparent myocardial involvement in scleroderma portends a very poor prognosis. One study of US veterans found that clinical cardiac disease in scleroderma was associated with a 70% mortality rate at five years. Management of heart failure and conduction system abnormalities in scleroderma is similar to other cardiac disease. It includes afterload reduction, beta-blockade, defibrillator placement, etc. Patients with reduced cardiac function and normal coronary arteries may benefit from increased immune suppresion.
文摘Non-typhoidal salmonellosis has emerged as an invasive infection in industrialized countries. Bacteremia and pleuropulmonary involvement usually occur in the setting of chronic illnesses such as diabetes, malignancies and HIV. We present three cases of non-typhoidal salmonellosis in immunocompetent patients presenting over a year period. A 66-year-old female presented with septic shock. She was started on vancomycin, doripenem and ciprofloxacin. Her blood cultures grew Salmonella enteridis that was also isolated from her urine and bronchoalveolar lavage fluid. Stool cultures were negative for Salmonella species. She had no epidemiologic risk factors for invasive Salmonella infection. Her immunodeficiency workup was negative. CT scan abdomen was unremarkable. She became hemodynamically stable and completed a two week course of Ceftriaxone without complications. A 58-year-old female presented with sub-acute onset of fever and dyspnea. CT chest showed bilateral pleural effusions. Left sided thoracentesis revealed purulent fluid consistent with empyema. Pleural fluid cultures grew Salmonella Group D. Blood, sputum and stool cultures remained negative. She denied consumption of raw eggs or exposure to pets, farm animals or reptiles. She was treated with Ceftriaxone for two weeks along with pigtail catheter drainage. Her immunodeficiency workup was negative. A 62-year-old man presented with acute left lower quadrant abdominal pain. CT Abdomen revealed a focal abnormality in abdominal aorta consistent with mycotic aneurysm. Blood cultures grew Salmonella Group D resistant to cephalosporins and bactrim, hence treatment with Meropenem was started. Subsequent blood, respiratory tract, urine and stool cultures remained negative. Due to high risk of perioperative complications, it was decided to follow the mycotic aneurysm expectantly. Antibiotics were deescalated to six weeks of Ertapenem followed by long term quinolone prophylaxis. He also did not have any epidemiologic risk factors for salmonellosis and his immunodeficiency workup was negative. These cases highlight the pathogenesis of this invasive organism that is transmitted though food borne route and causes bacteremic seeding of various sites such as lungs and pleura. It is extremely important to consider this organism in patients presenting with gram negative bacteremia leading to septic shock as well as endovascular infections.
文摘Background: Chronic obstructive pulmonary disease (COPD) and presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with endobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25 (11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Regression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age, gender and tobacco smoking. Results: Patients with FEV1% of <50% had 4.5 times greater risk of being diagnosed with an EPL [95% confidence interval: 1.93-10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥80. COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p = 0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among patients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with EPL who need more intense LC surveillance.
文摘Traumatic Brain Injury is a major cause of death and long-term disability.The early identification of patients at high risk of mortality is important for both management and prognosis.Although many modified scoring systems have been developed for improving the prediction accuracy in patients with trauma,few studies have focused on prediction accuracy and application in patients with traumatic brain injury.The shock index(SI)which was first introduced in the 1960s has shown to strongly correlate degree of circulatory shock with increasing SI.In this editorial we comment on a publication by Carteri et al wherein they perform a retrospective analysis studying the predictive potential of SI and its variants in populations with severe traumatic brain injury.
文摘Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States.While community-acquired pneumonia(CAP)is generally considered an acute time-limited illness,it is associated with high long-term mortality,with nearly one-third of patients requiring hospitalization dying within one year.An increasing trend of detecting multidrug-resistant(MDR)organisms causing CAP has been observed,especially in the Western world.In this editorial,we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia,bacteremia,and infective endocarditis that led to the patient’s death.The early detection of these resistant organisms helps improve patient outcomes.Significant advances have been made in the biotechnological and research space,but preventive measures,diagnostic techniques,and treatment strategies need to be developed.
文摘Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.
文摘Obesity, sleep apnea, diabetes and cardiovascular diseases are some of the most common diseases encountered by the worldwide population, with high social and economic burdens. Significant emphasis has been placed on obtaining blood pressure, body mass index, and placing importance on screening for signs and symptoms pointing towards cardiovascular disease. Symptoms related to sleep, or screening for sleep apnea has been overlooked by cardiac, diabetic, pulmonary and general medicine clinics despite recommendations for screening by several societies. In recent years, there is mounting data where obesity and obstructive sleep apnea sit at the epicenter and its control can lead to improvement and prevention of diabetes and cardiovascular complications. This editorial raises questions as to why obstructive sleep apnea screening should be included as yet another vital sign during patient initial inpatient or outpatient visit.
基金supported in part by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health, USA (R01HL111656 and K23HL098454 to RFM)the Pulmonary Hypertension Association Proof-of-Concept Research Grant (to J.C.)
文摘Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global sodium consumption greatly exceeds guidelines recommended by all medical institutions. This review synthesizes the data of landmark mammalian and human studies which investigated the role of sodium in the pathogenesis of hypertension, along with modern studies questioning this relationship. Recent studies concerning the potential pathways by which high-sodium concentration induces hypertension were reviewed. Human trials and population studies revealed a strong correlation between high blood pressure and average dietary sodium; and animal studies found a dramatic reduction in vascular function in a variety of mammals treated with high-sodium diets. In spite of a few contrarian studies, we found overwhelming evidence that elevated sodium consumption could cause hypertension
