BACKGROUND Significant gaps in guideline-directed medical therapy(GDMT)for heart failure(HF)stem from shortages of cardiologists and advanced HF providers,as well as a lack of optimal HF management knowledge among hos...BACKGROUND Significant gaps in guideline-directed medical therapy(GDMT)for heart failure(HF)stem from shortages of cardiologists and advanced HF providers,as well as a lack of optimal HF management knowledge among hospitalists.This study compared the impact of optimal medical therapy in HF(OMT-HF)certification on GDMT implementation and patient outcomes between an intervention group(IG)of hospitalists and a standard-of-care comparison group(SOC-CG).METHODS This study was implemented from November 2022 to May 2023.Hospitalized car-diology patients with HF and left ventricular ejection fraction≤40%were rando-mized to IG or SOC-CG.Exclusion criteria included patients in cardiogenic shock,unable to consent,or at high risk.Follow-up was at 30 days post-discharge.Diffe-rences between groups were analyzed using Fisher’s exact test for categorical va-riables and Wilcoxon rank-sum or unpaired t-test for continuous variables.Chan-ges in Minnesota Living with Heart Failure Questionnaire(MLWHFQ)scores were evaluated using a paired t-test.RESULTS IG patients had lower readmission rates[9(42.85%)vs 11(17.46%),P=0.03]and a decreased trend in mortality 30-day post discharge.IG patients also showed greater mean improvements in total(-27.03±24.59 vs-5.85±23.52,P<0.001),physical(-13.8±12.3 vs-2.71±11.16,P<0.001)and emotional(-4.76±8.10 vs-1.42±5.98)dimensions on the MLWHFQ compared to SOC-CG,however,change in emotional dimension did not reach statistical significance.CONCLUSION Hospitalist OMT-HF certification may lead to better 30-day outcomes in hospitalized HF patients including quality of life,mortality and readmission rates.Larger prospective studies are warranted to validate these findings.展开更多
Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)...Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)introduced the Single Tremelimumab Regular Interval Durvalumab(STRIDE)regimen,an immunotherapy-based approach that achieved a median overall survival(OS)of 16.43 months compared to 13.77 months with sorafenib.While statistically significant,this~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost.This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC,alongside other regimens such as atezolizumab plus bevacizumab and nivolumab plus ipilimumab.We explore STRIDE’s mechanism of action,safety profile,modest progression-free survival(PFS)improvement,and implementation challenges,incorporating insights from 2023-2025 research.In addition,we discussed its limitations in non-viral HCC and Child-Pugh B patients,the role of emerging biomarkers,and the potential of radiation to enhance immunotherapy efficacy.As a dual immune checkpoint inhibitor(ICI)strategy,STRIDE offers an important advance that may not only extend survival but also open the door to future curative approaches.However,optimizing its use will require refined patient selection and further investigation of synergistic combination therapies.展开更多
Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formul...Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.展开更多
BACKGROUND Metabolic dysfunction-associated steatohepatitis(MASH)is increasingly common,as is hepatocellular carcinoma(HCC)in the background of MASH.Liver transplantation(LT)provides superior long-term survival for pa...BACKGROUND Metabolic dysfunction-associated steatohepatitis(MASH)is increasingly common,as is hepatocellular carcinoma(HCC)in the background of MASH.Liver transplantation(LT)provides superior long-term survival for patients with unresectable MASH-HCC,but not all patients have equal access to transplant.MASH-HCC disproportionately affects Hispanic patients,but minorities are less likely to undergo LT for HCC.Additionally,females also undergo LT at lower rates than males.AIM To investigate whether race/ethnicity and sex affect LT waitlist outcomes.METHODS Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed.RESULTS Most of the 3810 patients waitlisted for LT for MASH-HCC were non-Hispanic(NH)white(71.2%)or Hispanic(23.4%),with only 49(1.1%)NH Black candidates.Hispanics underwent LT at lower rates than NH whites(71.6%vs 78.4%,P<0.001),but race/ethnicity did not affect waitlist mortality(P=0.06).Patients with Hispanic[hazard ratio(HR)=0.85,95%CI:0.77-0.95,P=0.002]or Asian(HR=0.79,95%CI:0.63-0.98,P=0.04)race/ethnicity were less likely to undergo LT.Women were also less likely to receive LT(male:HR=1.16,95%CI:1.04-1.29,P=0.01).Patients in regions 1 and 9 were less likely to be transplanted as well(P=0.07).CONCLUSION Hispanic patients are less likely to undergo LT for MASH-HCC,concerning given their susceptibility to MASH and HCC.There were very few NH Black candidates.Disparities were also unequal across regions,which is particularly concerning in states where at-risk populations have rising cancer incidence.Additional research is needed to identify strategies for mitigating these differences in access to LT for MASH-HCC.展开更多
Objectives Salpingectomy and tubal ligation are commonly performed for permanent contraception in women.Salpingectomy has been suggested to reduce the risk of ovarian cancer,but its comparative operative and periopera...Objectives Salpingectomy and tubal ligation are commonly performed for permanent contraception in women.Salpingectomy has been suggested to reduce the risk of ovarian cancer,but its comparative operative and perioperative risks have not been well established.The objective of this study is to compare the peri-and postoperative complications of laparoscopic tubal ligation with those of salpingectomy for permanent contraception.Methods A retrospective review of 49,445 patients who underwent laparoscopic salpingectomy or tubal ligation for permanent contraception between 2017 and 2021 was conducted using data from the American College of Surgeons National Surgical Quality Improvement Program database.Statistical analysis involved t test,chi-square test,and logistic regression analysis with the use of the random forest algorithm.The primary outcomes were perioperative and postoperative complications.Results Of the total cohort,45,307(91.6%)underwent laparoscopic salpingectomy,and 4138(8.4%)received laparoscopic tubal ligation.There were significant differences between the salpingectomy and tubal ligation groups with respect to several demographic characteristics,including age,BMI,minority status,and variations in past medical history.These demographic characteristics were controlled for in the multivariate regression analysis.Salpingectomy had a higher rate of operative and postoperative complications than did tubal ligation(OR=1.78,95%CI:1.46-2.20,p<0.001).Salpingectomy was associated with a greater risk of longer operation time(OR=2.03,95%CI:2.02-2.04,p<0.001),longer hospital stay(OR=5.26,95%CI:4.57-6.09,p<0.001),increased readmission(OR=3.15,95%CI:1.92-5.65,p<0.001),and increased unplanned reoperation(OR=2.42,95%CI:1.32-5.12,p=0.010).In addition,the occurrence rates of organ space surgical site infection(OR=2.68,95%CI:1.21-7.59,p=0.032)and sepsis(OR=3.93,95%CI:1.48-16.02,p=0.020)were significantly greater in the salpingectomy group than in the tubal ligation group.Conclusions Laparoscopic tubal ligation and salpingectomy are both safe and effective procedures for permanent contraception;however,salpingectomy is more likely to be associated with peri-and postoperative complications.These findings may help guide clinical decision-making when selecting the optimal permanent contraception method for women.展开更多
Locally advanced non-small cell lung cancer(NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is signiicant interest in inding more biologically active ch...Locally advanced non-small cell lung cancer(NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is signiicant interest in inding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled "PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer", compared two diferent chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received consolidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no diference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not ofer a clinical advantage over standard cisplatin plus etoposide. There are some subpopulations who might still beneit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.展开更多
The incidence of biliary injury after laparoscopic cholecystectomy(LC) has shown a declining trend though it may still be twice that as with open cholecystectomy. Major biliary or vasculobiliary injury is associated w...The incidence of biliary injury after laparoscopic cholecystectomy(LC) has shown a declining trend though it may still be twice that as with open cholecystectomy. Major biliary or vasculobiliary injury is associated with significant morbidity. As prevention is the best strategy, the concept of a culture of safe cholecystectomy has been recently introduced to educate surgeons and apprise them of basic tenets of safe performance of LC. Various aspects of safe cholecystectomy include:(1) thorough knowledge of relevant anatomy, various anatomical landmarks, and anatomical variations;(2) an understanding of the mechanisms involved in biliary/vascular injury, the most important being the misidentification injury;(3) identification of various preoperative and intraoperative predictors of difficult cholecystectomy;(4) proper gallbladder retraction;(5) safe use of various energy devices;(6) understanding the critical view of safety, including its doublet view and documentation;(7) awareness of various error traps(e.g., fundus first technique);(8) use of various bailout strategies(e.g., subtotal cholecystectomy) in difficult gallbladder cases;(9) use of intraoperative imaging techniques(e.g., intraoperative cholangiogram) to ascertain correct anatomy; and(10) understanding the concept of time-out.Surgeons should be facile with these aspects of this culture of safety in cholecystectomy in an attempt to reduce the incidence of biliary/vascular injury during LC.展开更多
Glycogenic hepatopathy(GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the rever...Glycogenic hepatopathy(GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease(NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.展开更多
Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and...Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.展开更多
Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to...Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.展开更多
AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research...AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.展开更多
AIM To determine if topical application of platelet-rich plasma(PRP) to diabetic foot ulcers(DFUs) results in superior healing rates. METHODS A systematic review was registered with PROSPERO and performed using PRISMA...AIM To determine if topical application of platelet-rich plasma(PRP) to diabetic foot ulcers(DFUs) results in superior healing rates. METHODS A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level Ⅰ-Ⅳ investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were "platelet rich plasma", "diabetes", "ulcers", and "wound". The Modified Coleman Methodology Score(MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.RESULTS One thousand two hundred and seventeen articles were screened. Eleven articles(322 PRP subjects, 126 controls, PRP subject mean age 58.4 ± 7.2 years, control mean age 58.7 ± 5.9 years) were analyzed. Six articles were level Ⅱ evidence, four were level Ⅲ, and one article was level Ⅳ. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls(0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). Mean heal time to > 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively(P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls(7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P < 0.001).CONCLUSION The topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls.展开更多
As surgical techniques continue to move towards less invasive techniques,single incision laparoscopic surgery(SILS),a hybrid between traditional multiport laparoscopy and natural orifice transluminal endoscopic surger...As surgical techniques continue to move towards less invasive techniques,single incision laparoscopic surgery(SILS),a hybrid between traditional multiport laparoscopy and natural orifice transluminal endoscopic surgery,was introduced to further the enhanced outcomes of multiport laparoscopy. The safety and feasibility of SILS for both benign and malignant colorectal disease has been proven. SILS provides the potential for improved cosmesis,postoperative pain,recovery time,and quality of life at the drawback of higher technical skill required. In this article,we review the history,describe the available technology and techniques,and evaluate the benefits and limitations of SILS for colorectal surgery in the published literature.展开更多
Adenoid cystic carcinoma(ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most b...Adenoid cystic carcinoma(ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features(i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features.展开更多
Single incision laparoscopic surgery(SILS) is a minimally invasive platform with specific benefits over traditional multiport laparoscopic surgery. The safety and feasibility of SILS has been proven, and the applicati...Single incision laparoscopic surgery(SILS) is a minimally invasive platform with specific benefits over traditional multiport laparoscopic surgery. The safety and feasibility of SILS has been proven, and the applications continue to grow with experience. After 500 cases at a high-volume, single-institution, we were able to standardize instrumentation and operative steps, as well as develop adaptations in technique to help overcome technical and ergonomic challenges. These technical adaptations have allowed the successful application of SILS to technically difficult patient populations, such as pelvic cases, inflammatory bowel disease cases, and high body mass index patients. This review is a frame of reference for the application and wider integration of the single incision laparoscopic platform in colorectal surgery.展开更多
By altering the electrostatic charge of histones or providing binding sites to protein recognition molecules, Chromatin marks have been proposed to regulate gene expression, a property that has motivated researchers t...By altering the electrostatic charge of histones or providing binding sites to protein recognition molecules, Chromatin marks have been proposed to regulate gene expression, a property that has motivated researchers to link these marks to cis-regulatory elements. With the help of next generation sequencing technologies, we can now correlate one specific chromatin mark with regulatory elements (e.g. enhancers or promoters) and also build tools, such as hidden Markov models, to gain insight into mark combinations. However, hidden Markov models have limitation for their character of generative models and assume that a current observation depends only on a current hidden state in the chain. Here, we employed two graphical probabilistic models, namely the linear conditional random field model and multivariate hidden Markov model, to mark gene regions with different states based on recurrent and spatially coherent character of these eight marks. Both models revealed chromatin states that may correspond to enhancers and promoters, transcribed regions, transcriptional elongation, and low-signal regions. We also found that the linear conditional random field model was more effective than the hidden Markov model in recognizing regulatory elements, such as promoter-, enhancer-, and transcriptional elongation-associated regions, which gives us a better choice.展开更多
基金Supported by Houston Methodist DeBakey Heart and Vascular Center Grant.
文摘BACKGROUND Significant gaps in guideline-directed medical therapy(GDMT)for heart failure(HF)stem from shortages of cardiologists and advanced HF providers,as well as a lack of optimal HF management knowledge among hospitalists.This study compared the impact of optimal medical therapy in HF(OMT-HF)certification on GDMT implementation and patient outcomes between an intervention group(IG)of hospitalists and a standard-of-care comparison group(SOC-CG).METHODS This study was implemented from November 2022 to May 2023.Hospitalized car-diology patients with HF and left ventricular ejection fraction≤40%were rando-mized to IG or SOC-CG.Exclusion criteria included patients in cardiogenic shock,unable to consent,or at high risk.Follow-up was at 30 days post-discharge.Diffe-rences between groups were analyzed using Fisher’s exact test for categorical va-riables and Wilcoxon rank-sum or unpaired t-test for continuous variables.Chan-ges in Minnesota Living with Heart Failure Questionnaire(MLWHFQ)scores were evaluated using a paired t-test.RESULTS IG patients had lower readmission rates[9(42.85%)vs 11(17.46%),P=0.03]and a decreased trend in mortality 30-day post discharge.IG patients also showed greater mean improvements in total(-27.03±24.59 vs-5.85±23.52,P<0.001),physical(-13.8±12.3 vs-2.71±11.16,P<0.001)and emotional(-4.76±8.10 vs-1.42±5.98)dimensions on the MLWHFQ compared to SOC-CG,however,change in emotional dimension did not reach statistical significance.CONCLUSION Hospitalist OMT-HF certification may lead to better 30-day outcomes in hospitalized HF patients including quality of life,mortality and readmission rates.Larger prospective studies are warranted to validate these findings.
文摘Unresectable hepatocellular carcinoma(HCC)remains a global challenge,with limited effective treatment options for advanced-stage disease.The HIMALAYA trial(phase III randomized study that evaluated the STRIDE regimen)introduced the Single Tremelimumab Regular Interval Durvalumab(STRIDE)regimen,an immunotherapy-based approach that achieved a median overall survival(OS)of 16.43 months compared to 13.77 months with sorafenib.While statistically significant,this~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost.This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC,alongside other regimens such as atezolizumab plus bevacizumab and nivolumab plus ipilimumab.We explore STRIDE’s mechanism of action,safety profile,modest progression-free survival(PFS)improvement,and implementation challenges,incorporating insights from 2023-2025 research.In addition,we discussed its limitations in non-viral HCC and Child-Pugh B patients,the role of emerging biomarkers,and the potential of radiation to enhance immunotherapy efficacy.As a dual immune checkpoint inhibitor(ICI)strategy,STRIDE offers an important advance that may not only extend survival but also open the door to future curative approaches.However,optimizing its use will require refined patient selection and further investigation of synergistic combination therapies.
基金This study was reviewed and approved by the New York-Presbyterian Brooklyn Methodist Hospital Institutional Review Committee.The study follows the guidelines outlined in the Declaration of Helsinki.
文摘Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.
文摘BACKGROUND Metabolic dysfunction-associated steatohepatitis(MASH)is increasingly common,as is hepatocellular carcinoma(HCC)in the background of MASH.Liver transplantation(LT)provides superior long-term survival for patients with unresectable MASH-HCC,but not all patients have equal access to transplant.MASH-HCC disproportionately affects Hispanic patients,but minorities are less likely to undergo LT for HCC.Additionally,females also undergo LT at lower rates than males.AIM To investigate whether race/ethnicity and sex affect LT waitlist outcomes.METHODS Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed.RESULTS Most of the 3810 patients waitlisted for LT for MASH-HCC were non-Hispanic(NH)white(71.2%)or Hispanic(23.4%),with only 49(1.1%)NH Black candidates.Hispanics underwent LT at lower rates than NH whites(71.6%vs 78.4%,P<0.001),but race/ethnicity did not affect waitlist mortality(P=0.06).Patients with Hispanic[hazard ratio(HR)=0.85,95%CI:0.77-0.95,P=0.002]or Asian(HR=0.79,95%CI:0.63-0.98,P=0.04)race/ethnicity were less likely to undergo LT.Women were also less likely to receive LT(male:HR=1.16,95%CI:1.04-1.29,P=0.01).Patients in regions 1 and 9 were less likely to be transplanted as well(P=0.07).CONCLUSION Hispanic patients are less likely to undergo LT for MASH-HCC,concerning given their susceptibility to MASH and HCC.There were very few NH Black candidates.Disparities were also unequal across regions,which is particularly concerning in states where at-risk populations have rising cancer incidence.Additional research is needed to identify strategies for mitigating these differences in access to LT for MASH-HCC.
文摘Objectives Salpingectomy and tubal ligation are commonly performed for permanent contraception in women.Salpingectomy has been suggested to reduce the risk of ovarian cancer,but its comparative operative and perioperative risks have not been well established.The objective of this study is to compare the peri-and postoperative complications of laparoscopic tubal ligation with those of salpingectomy for permanent contraception.Methods A retrospective review of 49,445 patients who underwent laparoscopic salpingectomy or tubal ligation for permanent contraception between 2017 and 2021 was conducted using data from the American College of Surgeons National Surgical Quality Improvement Program database.Statistical analysis involved t test,chi-square test,and logistic regression analysis with the use of the random forest algorithm.The primary outcomes were perioperative and postoperative complications.Results Of the total cohort,45,307(91.6%)underwent laparoscopic salpingectomy,and 4138(8.4%)received laparoscopic tubal ligation.There were significant differences between the salpingectomy and tubal ligation groups with respect to several demographic characteristics,including age,BMI,minority status,and variations in past medical history.These demographic characteristics were controlled for in the multivariate regression analysis.Salpingectomy had a higher rate of operative and postoperative complications than did tubal ligation(OR=1.78,95%CI:1.46-2.20,p<0.001).Salpingectomy was associated with a greater risk of longer operation time(OR=2.03,95%CI:2.02-2.04,p<0.001),longer hospital stay(OR=5.26,95%CI:4.57-6.09,p<0.001),increased readmission(OR=3.15,95%CI:1.92-5.65,p<0.001),and increased unplanned reoperation(OR=2.42,95%CI:1.32-5.12,p=0.010).In addition,the occurrence rates of organ space surgical site infection(OR=2.68,95%CI:1.21-7.59,p=0.032)and sepsis(OR=3.93,95%CI:1.48-16.02,p=0.020)were significantly greater in the salpingectomy group than in the tubal ligation group.Conclusions Laparoscopic tubal ligation and salpingectomy are both safe and effective procedures for permanent contraception;however,salpingectomy is more likely to be associated with peri-and postoperative complications.These findings may help guide clinical decision-making when selecting the optimal permanent contraception method for women.
文摘Locally advanced non-small cell lung cancer(NSCLC) continues to be a challenging disease to treat. With high rates of both local and distant failures, there is signiicant interest in inding more biologically active chemotherapy regimens that can contribute to reduce both failures. The phase III PROCLAIM trial, recently published in the Journal of Clinical Oncology entitled "PROCLAIM: randomized phase III trial of pemetrexed–cisplatin or etoposide–cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer", compared two diferent chemotherapy regimens given concurrently with radiotherapy in patients with stage III non-squamous lung cancer: pemetrexed plus cisplatin versus cisplatin plus etoposide. Both groups received consolidation chemotherapy. After enrolling 598 of planned 600 patients, the study was stopped early due to futility as no diference was seen in the primary end-point of overall survival. Since PROCLAIM was designed as a superiority trial, these results suggest that pemetrexed regimens do not ofer a clinical advantage over standard cisplatin plus etoposide. There are some subpopulations who might still beneit from pemetrexed, especially if clinicians are concerned about myelosuppression-related adverse events. Future trials are needed to investigate novel biologic agents and irradiation techniques that can result in more durable local and distant disease control in locally advanced NSCLC.
文摘The incidence of biliary injury after laparoscopic cholecystectomy(LC) has shown a declining trend though it may still be twice that as with open cholecystectomy. Major biliary or vasculobiliary injury is associated with significant morbidity. As prevention is the best strategy, the concept of a culture of safe cholecystectomy has been recently introduced to educate surgeons and apprise them of basic tenets of safe performance of LC. Various aspects of safe cholecystectomy include:(1) thorough knowledge of relevant anatomy, various anatomical landmarks, and anatomical variations;(2) an understanding of the mechanisms involved in biliary/vascular injury, the most important being the misidentification injury;(3) identification of various preoperative and intraoperative predictors of difficult cholecystectomy;(4) proper gallbladder retraction;(5) safe use of various energy devices;(6) understanding the critical view of safety, including its doublet view and documentation;(7) awareness of various error traps(e.g., fundus first technique);(8) use of various bailout strategies(e.g., subtotal cholecystectomy) in difficult gallbladder cases;(9) use of intraoperative imaging techniques(e.g., intraoperative cholangiogram) to ascertain correct anatomy; and(10) understanding the concept of time-out.Surgeons should be facile with these aspects of this culture of safety in cholecystectomy in an attempt to reduce the incidence of biliary/vascular injury during LC.
文摘Glycogenic hepatopathy(GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease(NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.
文摘Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.
文摘Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.
文摘AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.
文摘AIM To determine if topical application of platelet-rich plasma(PRP) to diabetic foot ulcers(DFUs) results in superior healing rates. METHODS A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level Ⅰ-Ⅳ investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were "platelet rich plasma", "diabetes", "ulcers", and "wound". The Modified Coleman Methodology Score(MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.RESULTS One thousand two hundred and seventeen articles were screened. Eleven articles(322 PRP subjects, 126 controls, PRP subject mean age 58.4 ± 7.2 years, control mean age 58.7 ± 5.9 years) were analyzed. Six articles were level Ⅱ evidence, four were level Ⅲ, and one article was level Ⅳ. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls(0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). Mean heal time to > 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively(P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls(7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P < 0.001).CONCLUSION The topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls.
文摘As surgical techniques continue to move towards less invasive techniques,single incision laparoscopic surgery(SILS),a hybrid between traditional multiport laparoscopy and natural orifice transluminal endoscopic surgery,was introduced to further the enhanced outcomes of multiport laparoscopy. The safety and feasibility of SILS for both benign and malignant colorectal disease has been proven. SILS provides the potential for improved cosmesis,postoperative pain,recovery time,and quality of life at the drawback of higher technical skill required. In this article,we review the history,describe the available technology and techniques,and evaluate the benefits and limitations of SILS for colorectal surgery in the published literature.
文摘Adenoid cystic carcinoma(ACC) of the breast is a rare special subtype of breast cancer characterized by the presence of a dual cell population of luminal and basaloid cells arranged in specific growth patterns. Most breast cancers with triple-negative, basal-like breast features(i.e., tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers) are generally high-grade tumors with an aggressive clinical course. Conversely, while ACCs also display a triple-negative, basal-like phenotype, they are usually low-grade and exhibit an indolent clinical behavior. Many discoveries regarding the molecular and genetic features of the ACC, including a specific chromosomal translocation t(6;9) that results in a MYB-NFIB fusion gene, have been made in recent years. This comprehensive review provides our experience with ACC of the breast, as well as an overview of clinical, histopathological, and molecular genetic features.
文摘Single incision laparoscopic surgery(SILS) is a minimally invasive platform with specific benefits over traditional multiport laparoscopic surgery. The safety and feasibility of SILS has been proven, and the applications continue to grow with experience. After 500 cases at a high-volume, single-institution, we were able to standardize instrumentation and operative steps, as well as develop adaptations in technique to help overcome technical and ergonomic challenges. These technical adaptations have allowed the successful application of SILS to technically difficult patient populations, such as pelvic cases, inflammatory bowel disease cases, and high body mass index patients. This review is a frame of reference for the application and wider integration of the single incision laparoscopic platform in colorectal surgery.
基金funded by grants from the NIH R01LM010185-03(Zhou),NIH U01HL111560-01(Zhou),NIH 1R01DE022676-01(Zhou),and DoD TATRC (Zhou)
文摘By altering the electrostatic charge of histones or providing binding sites to protein recognition molecules, Chromatin marks have been proposed to regulate gene expression, a property that has motivated researchers to link these marks to cis-regulatory elements. With the help of next generation sequencing technologies, we can now correlate one specific chromatin mark with regulatory elements (e.g. enhancers or promoters) and also build tools, such as hidden Markov models, to gain insight into mark combinations. However, hidden Markov models have limitation for their character of generative models and assume that a current observation depends only on a current hidden state in the chain. Here, we employed two graphical probabilistic models, namely the linear conditional random field model and multivariate hidden Markov model, to mark gene regions with different states based on recurrent and spatially coherent character of these eight marks. Both models revealed chromatin states that may correspond to enhancers and promoters, transcribed regions, transcriptional elongation, and low-signal regions. We also found that the linear conditional random field model was more effective than the hidden Markov model in recognizing regulatory elements, such as promoter-, enhancer-, and transcriptional elongation-associated regions, which gives us a better choice.
