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BACKGROUND & AIMS: Preoperative risk stratification may help guide prophylactic biologic utilization for the prevention of postoperative Crohn's disease (CD) recurrence; however, there are limited data exploring and validating proposed clinical risk factors. We aimed to explore the preoperative clinical risk profiles, quantify individual risk factors, and assess the impact of biologic prophylaxis on postoperative recurrence risk in a real-world cohort. METHODS: In this multicenter retrospective analysis, patients with CD who underwent ileocolonic resection (ICR) from 2009 to 2020 were identified. High-risk (active smoking, ≥2 prior surgeries, penetrating disease, and/or perianal disease) and low-risk (nonsmokers and age >50 y) features were used to stratify patients. We assessed the risk of endoscopic (Rutgeert score, ≥i2b) and surgical recurrence by risk strata and biologic prophylaxis (≤90 days postoperatively) with logistic and time-to-event analyses. RESULTS: A total of 1404 adult CD patients who underwent ICR were included. Of the high-risk factors, 2 or more ICRs (odds ratio [OR], 1.71; 95% CI, 1.13-2.57), active smoking (OR, 1.73; 95% CI, 1.17-2.53), penetrating disease (OR, 1.41; 95% CI, 1.02-1.94), and history of perianal disease alone (OR, 1.99; 95% CI, 1.42-2.79) were associated with surgical but not endoscopic recurrence. Surgical recurrence was lower in high-risk patients receiving prophylaxis vs not (10.2% vs 16.7%; P = .02), and endoscopic recurrence was lower in those receiving prophylaxis irrespective of risk strata (high-risk, 28.1% vs 37.4%; P = .03; and low-risk, 21.1% vs 38.3%; P = .002). CONCLUSIONS: Clinical risk factors accurately illustrate patients at risk for surgical recurrence, but have limited utility in predicting endoscopic recurrence. Biologic prophylaxis may be of benefit irrespective of risk stratification and future studies should assess this.
Subject(s)
Biological Products , Crohn Disease , Adult , Humans , Crohn Disease/prevention & control , Crohn Disease/surgery , Crohn Disease/drug therapy , Retrospective Studies , Endoscopy/adverse effects , Risk Factors , Biological Products/therapeutic use , Recurrence , Ileum/surgeryABSTRACT
Hypertrophic cardiomyopathy (HCM) is a phenotypically heterogeneous disease with a genetic basis and variable penetrance. The hallmarks of HCM include dynamic left ventricular outflow tract obstruction, typically caused by asymmetric septal hypertrophy. However, abnormal papillary muscle placement, abnormal mitral valve and subvalvular apparatus and apical hypertrophic forms have also been described. Typical medical treatment has been stagnant for decades, although there have been significant advances in surgical treatment of patients with obstructive HCM. Herein, we describe a new class of drugs targeting the specific pathophysiology of HCM.
Hypertrophic obstructive cardiomyopathy is a genetic condition that leads to increased heart muscle size. This increase in heart muscle can cause blockage of appropriate blood flow out of the heart. In such cases, current medications like ß-blockers, calcium channel blockers and disopyramide can be used, but do not directly target the problem of increased heart muscle size. A new medication class, cardiac myosin inhibitors, decrease the squeezing power of the increased heart muscle to allow for more appropriate blood flow out of the heart. So far, trials have been conducted with mavacamten, with upcoming trials of aficamten (another novel cardiac myosin inhibitor). Recent trials with mavacamten have shown that this medication class has been beneficial for patients in whom other medications have failed. Some trials have also shown that by taking cardiac myosin inhibitors, patients have been able to avoid or delay surgery to correct this problem. Reassuringly, short-term data for this class of medications are positive. However, given that these medications are new, continued monitoring and research is being done to evaluate their long-term effect.
Subject(s)
Cardiomyopathy, Hypertrophic, Familial , Cardiomyopathy, Hypertrophic , Heart Valve Diseases , Ventricular Outflow Obstruction, Left , Humans , Cardiomyopathy, Hypertrophic/therapyABSTRACT
GOALS: Assess the outcomes of various therapeutic regimens to treat initial endoscopic postoperative recurrence despite biologic prophylaxis. BACKGROUND: Postoperative biologic prophylaxis reduces postoperative Crohn's disease (CD) recurrence rates. Optimal treatment strategies for endoscopic recurrence have not been elucidated. STUDY: Retrospective cohort study of adult CD patients who underwent ileocolonic resection between 2009 and 2020. Patients with endoscopic postoperative recurrence despite prophylactic biologic therapy and ≥1 subsequent colonoscopy were included. Treatment changes after recurrence were categorized as (1) therapy optimization or continuation or (2) new biologic class. The primary outcome was composite endoscopic or surgical recurrence at the time of or prior to subsequent follow-up colonoscopy. RESULTS: Eighty-one CD patients with endoscopic recurrence (54.3% i2b, 22.2% i3, and 23.5% i4) despite biologic prophylaxis (86.4% anti-tumor necrosis factor, 8.6% vedolizumab, 4.9% ustekinumab) were included. Most patients received therapy optimization or continuation (76.3%, n=61) following recurrence compared to being started on a new biologic class. Sixty patients (N=48 therapy optimization; N=12 new biologic class) experienced composite recurrence (78.3% endoscopic, 21.7% surgical). On multivariable modeling, initiation of a new biologic class was associated with reduced risk for composite recurrence compared to therapy optimization or continuation (aOR: 0.26; P=0.04). Additionally, initiation of a new biologic class was associated with endoscopic improvement when adjusting for endoscopic severity at the time of recurrence (aOR: 3.4; P=0.05). On sensitivity analysis, a new biologic class was associated or trended with improved rates of endoscopic healing and composite recurrence when directly compared to therapy optimization or continuation. CONCLUSION: In patients with CD who experience endoscopic recurrence despite biologic prophylaxis, changing the mechanism of biologic action may promote endoscopic improvement.
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In a large screening program of asymptomatic middle-aged individuals, we sought to assess the degree of risk reclassification provided by comparing multiethnic study on subclinical atherosclerosis coronary artery calcium scoring (CACS) versus atherosclerotic cardiovascular disease (ASCVD) and Reynolds risk score (RRS) score. All 5,324 consecutive patients (aged 57 ± 8 years, 76% male) who underwent CACS screening at the Cleveland Clinic as part of a primary prevention executive health between March 16 and October 21 were included. The 10-year ASCVD, RRS, and multiethnic study on subclinical atherosclerosis CACS (MESA-CACS) risk scores were calculated and categorized as <1, 1 to 4.99, 5 to 9.99, and ≥10%. Compared with ASCVD, using MESA-CACS resulted in a downgraded risk in 1,667 subjects (31%), whereas 738 (14%) had an upgrade in risk (total of 45% reclassification). Similarly, compared with RRS, using MESA-CACS resulted in an upgraded risk in 797 (15%) and a downgrade in 1,380 (26%) subjects (total of 41% reclassification). However, by further dividing by the distribution of the coronary calcification, ASCVD overestimates the risk only for patients with coronary artery calcium (CAC) in 0 or 1 coronary artery only, whereas MESA-CACS overestimates if the CAC was noted in ≥2 arteries. Similarly, RRS only overestimates the risk for patients with 0 CAC, whereas it underestimates the risk for patients with any CAC. In conclusion, the use of MESA-CACS, along with CAC distribution in primary prevention clinics, results in differential and significant reclassification of traditional scores when calculating the 10-years coronary vascular disease risk. Overall, RRS underestimates and ASCVD overestimates the cardiovascular disease risk compared with MESA-CACS.
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Atherosclerosis , Cardiovascular Diseases , Coronary Artery Disease , Vascular Calcification , Middle Aged , Humans , Male , Female , Coronary Artery Disease/epidemiology , Calcium , Coronary Vessels/diagnostic imaging , Risk Assessment/methods , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Risk Factors , Primary PreventionABSTRACT
PURPOSE: Transthyretin cardiac amyloidosis (ATTR-CA) is thought to be prevalent in patients with severe aortic stenosis (AS) who are referred for transcatheter aortic valve replacement (TAVR). However, prior studies were published when TAVR was only offered to elderly, inoperable, and high-risk patients. The aim of this study was to reevaluate the prevalence of ATTR-CA in a contemporary TAVR population and identify high-risk features to guide referral for technetium-99 pyrophosphate scan (99mTc-PyP scan) screening. METHODS: Patients seen in a multidisciplinary TAVR clinic for severe AS 70 years and older were referred for a 99mTc-PyP scan to evaluate for ATTR-CA. The primary outcome was the percent with a positive scan. The discriminatory ability of high-risk features was assessed to develop a more judicious screening system. RESULTS: Over the study period, 380 patients underwent screening, and 20 patients (5.3%) had a positive scan, with 17 patients having confirmed ATTR-CA, 1 patient deferring confirmatory testing (combined 4.7%), 1 having light chain amyloidosis, and 1 negative on biopsy. Compared to other patient and echocardiographic measures, elevated NT-pro BNP (> 1000 ng/L) was the best discriminator on who should be referred for 99mTc-PyP scan screening, with a sensitivity of 90% and a negative predictive value of 99%. CONCLUSION: The prevalence of ATTR-CA may be lower in a contemporary TAVR population due to its expanded indication for low-risk patients. NT-pro BNP is a simple test that can improve screening yield and more judiciously guide screening for ATTR-CA in this at-risk population. Comparison of the original versus the proposed algorithm.
Subject(s)
Amyloid Neuropathies, Familial , Cardiomyopathies , Transcatheter Aortic Valve Replacement , Humans , Aged , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloid Neuropathies, Familial/epidemiology , Cardiomyopathies/diagnostic imaging , Prevalence , Radionuclide Imaging , PrealbuminABSTRACT
INTRODUCTION: Surgical management of Crohn's disease (CD) is common. Postoperative complications include anastomotic stricturing (AS). The natural history and risk factors for AS have not been elucidated. METHODS: A retrospective cohort study of patients with CD who underwent ileocolonic resection (ICR) with ≥1 postoperative ileocolonoscopy between 2009 and 2020. Postoperative ileocolonoscopies with corresponding cross-sectional imaging were evaluated for evidence of AS without neoterminal ileal extension. Severity of AS and endoscopic intervention at time of detection were collected. Primary outcome was development of AS. Secondary outcome was time to AS detection. RESULTS: A total of 602 adult patients with CD underwent ICR with postoperative ileocolonoscopy. Of these, 426 had primary anastomosis, and 136 had temporary diversion at time of ICR. Anastomotic configuration consisted of 308 side-to-side, 148 end-to-side, and 136 end-to-end. One hundred ten (18.3%) patients developed AS with median time of 3.2 years to AS detection. AS severity at time of detection was associated with need for repeat surgical resection for AS. On multivariable Cox proportional hazard regression, anastomotic configuration and temporary diversion were not associated with risk of or time to AS. Preoperative stricturing disease was associated with decreased time to AS (adjusted hazard ratio 1.8; P = 0.049). Endoscopic ileal recurrence before AS was not associated with subsequent AS detection. DISCUSSION: AS is a relatively common postoperative CD complication. Patients with previous stricturing disease behavior are at increased risk of AS. Anastomotic configuration, temporary diversion, and ileal CD recurrence do not increase risk of AS. Early detection and intervention for AS may help prevent progression to repeat ICR.
Subject(s)
Crohn Disease , Adult , Humans , Crohn Disease/surgery , Crohn Disease/complications , Ileostomy/adverse effects , Colon/surgery , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Retrospective Studies , Neoplasm Recurrence, Local/complications , Ileum/surgery , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Postoperative Complications/etiology , RecurrenceABSTRACT
Background: Healthcare system costs associated with bladder cancer treatment are among the highest of curable malignancies, and prognosis in advanced disease remains poor. This scoping review examines the worldwide status of bladder cancer research by systematically mapping publications, exploring research topics, support, gaps and limitations that need to be addressed. Methods: We searched the Web of Science database for publications using controlled vocabulary. Results were limited between 2000-2020, and were included in our study based on pre-specified eligibility criteria. Data used for analysis included author's names, country of affiliation, language, journal, citations, and funding. Analysis was conducted using Biblioshiny R and SPSS. Research topics were identified according to sub-filters of title words and strings pre-determined by authors. Results: 40,657 results were retrieved, of which 19,976 original articles and reviews met the pre-specified criteria. 92% of the publications originated from 20 countries and were included in the analysis. Trends show an increase across the world, most of which is due to increasing contributions from USA and China. An increase by 1000% in funded publications has been achieved. Studies focused on Surgery, Pathology, and Diagnosis, while Radiotherapy, Palliative care, quality of life and Epidemiology were the least described. Genetics had the most increase while being the most funded. GDP, incidence, prevalence and mortality were each significantly positively correlated with overall bladder cancer research output. Conclusion: This review described the evolution of bladder cancer research. It also identified significant gaps and limitations that need to be highlighted as priority areas for research investment.
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BACKGROUND: Significant tricuspid regurgitation (TR) is associated with poor outcome and high operative mortality resulting from late presentation. Yet, the optimal timing for intervention is unknown. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of echocardiographic parameters to inform early intervention in asymptomatic TR. METHODS: Using the Cleveland Clinic echocardiography database 2004 to 2018, the authors identified a consecutive cohort of asymptomatic patients with moderate to severe (3+) or severe (4+) TR. Quantitative TR and right heart parameters were retrospectively determined, and their prognostic utility for all-cause mortality was assessed. RESULTS: In 325 asymptomatic patients (mean age: 67.9 years; 79.4% female) with at least 3+ TR, there were 132 deaths (40.6%), with a median survival time of 9.9 years (95% CI: 7.9-12.7 years). By contrast, the median survival time in an age- and sex-matched cohort of symptomatic TR patients was 4.4 years (95% CI: 2.8-5.9 years). Among all the echocardiographic parameters evaluated, right ventricle free wall strain (RVFWS) and tricuspid regurgitant volume (RVol) were the strongest predictors of mortality in asymptomatic TR. The optimal discriminatory thresholds for these parameters were RVFWS <-19% and RVol >45 mL. The 5-year survival rates by number of risk factors (RF) were 93% (95% CI: 86%-96%), 65% (95% CI: 55%-74%), and 38% (95% CI: 26%-49%) for no RF, 1 RF, and both RFs, respectively. Compared with symptomatic TR, mortality was lower for asymptomatic TR with no RF (HR: 0.10; 95% CI: 0.04-0.29) or 1 RF (HR: 0.29; 95% CI: 0.14-0.58), but similar for asymptomatic TR with both RFs (HR: 1.11; 95% CI: 0.56-2.19). CONCLUSIONS: RVFWS and RVol are key prognostic markers that can be serially monitored to inform optimal timing of intervention for severe asymptomatic TR.
Subject(s)
Tricuspid Valve Insufficiency , Humans , Female , Aged , Male , Tricuspid Valve Insufficiency/surgery , Tricuspid Valve/diagnostic imaging , Retrospective Studies , Predictive Value of Tests , Echocardiography , Severity of Illness IndexABSTRACT
Background: The model for end-stage liver disease (MELD) has been widely used to predict the mortality and morbidity of various surgical procedures. Objectives: We aimed to correlate a high preoperative MELD score with adverse 30-day postoperative complications following radical cystectomy. Design and Methods: Patients who underwent elective, non-emergency radical cystectomy were identified from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2017. Patients were categorized according to a calculated MELD score. The primary outcomes of this study were 30-day postoperative mortality, morbidity, and length of hospital stay following radical cystectomy. For further sensitivity analysis, propensity score matching was used to yield a total of 1387 matched pairs and primary outcomes were also assessed in the matched cohort. Results: Compared with patients with a MELD < 10, those with MELD ⩾ 10 had significantly higher rates of mortality [odds ratio (OR) = 1.71, p = 0.004], major complications (OR = 1.42, p < 0.001), and prolonged hospital stay (OR = 1.29, p < 0.001) on multivariate analysis. Following risk-adjustment for race, propensity-matched groups revealed that patients with MELD score ⩾ 10 were significantly associated with higher mortality (OR = 1.85, p = 0.008), major complications (OR = 1.34, p < 0.001), yet similar length of hospital stay (OR = 1.17, p = 0.072). Conclusion: MELD score ⩾ 10 is associated with higher mortality and morbidity in patients undergoing radical cystectomy compared with lower MELD scores. Risk-stratification using MELD score may assist clinicians in identifying high-risk patients to provide adequate preoperative counseling, optimize perioperative conditions, and even consider nonsurgical alternatives.
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Background: Most Middle East and North Africa (MENA) countries record pancreatic cancer incidence rates that are above the world's average. Reducing this burden requires evidence-based policies. This bibliometric review aims to examine the status of pancreatic cancer research in the MENA world, while systematically categorising publications across cancer care pathways. Methods: We searched Scopus, Medline and PubMed for peer-reviewed publications related to both pancreatic cancer and MENA countries by using controlled vocabulary and keywords. The results were screened for duplicates and later included in the analysis based on preset eligibility criteria. A structured data extraction form was used to collect data related to each article, its methodology, its cancer care pathway, funding status and authorship. Results: A total of 5,848 publications resulted from our search, from which 1,098 articles remained after applying the eligibility criteria. Trends show a steady increase in pancreatic cancer research by MENA. Case reports are the most common, whereas a lack in high-evidence clinical studies as well as public health and epidemiological research was evident. Most studies were not funded and had no female contributions. Funding, if present, came mostly from foreign states. There exists a much greater focus in research on diagnosis and treatment among other cancer care pathways. Most MENA-based studies did not involve collaborations with other countries. Country gross domestic product and population are both correlated to the research output. Conclusion: This bibliometric analysis identified significant gaps and limitations in pancreatic cancer research in MENA countries. Vital domains requiring research investment have also been highlighted as a first step towards evidence-based health policies.
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Objective: To conduct a scoping review examining the status of prostate cancer research in Arab countries and systematically map publications across the cancer care pathway. Prostate cancer incidence has been rising in the Arab world and tackling its increasing burden will require evidence-based policies. Methods: We searched Medline, PubMed and Scopus for peer-reviewed publications related to both our research topic and countries of interest by using controlled vocabulary and keywords. Search results were limited for the period between 2000 and 2020, screened for duplicates, and then included in our study based on pre-specified eligibility criteria. We used a structured data extraction form to extract information related to the article, its methodology, its cancer care pathway, funding status, and authorship. Results: A total of 4142 publications were retrieved from our search, of which 874 articles remained after applying eligibility criteria. Trends show a steady increase in prostate cancer research in the Arab world. Most studies were focussed on diagnosis and treatment, whereas a lack in studies concerning screening and prevention, as well as epidemiological data, was evident. Most studies were not funded and had no female author. Country gross domestic product and population were positively correlated with its research output. The USA had the highest number of corresponding authors. The majority of Arab-based studies did not involve collaborations with other countries. Most research conducted was basic or clinical studies with a low level of evidence. Conclusion: Our present review identified significant gaps and limitations in prostate cancer research in Arab countries. Priority areas for research investment have also been highlighted as a first step towards context-specific health policies. Abbreviations: ASR: age-standardised rate; COVID-19: coronavirus disease 2019; GDP: gross domestic product; HDI: Human Development Index; KSA: Kingdom of Saudi Arabia; UAE: United Arab Emirates.
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Cardiovascular disease (CVD) remains the primary cause of global morbidity and mortality. CVD includes various life-threatening conditions such as myocardial infarction, stroke and peripheral arterial diseases. In this context, atherosclerosis continues to play the principal role in the pathogenesis of these conditions. Atherosclerosis emanates from a set of modifiable and non-modifiable risk factors that include age, male gender, family history, obesity, smoking, diabetes mellitus and hypertension. Recent evidence classifies atherosclerosis as a latent disease affecting all-sized arteries with a predilection for arterial branching points of decreased or absent blood supply. Atherosclerosis is not only a lipid metabolism disorder, but is also a chronic inflammatory one. This review providesa synoptic discussion of the underlying pathological mechanisms of atherosclerosis andthe currently applied therapeutic interventions. We then discuss the classical lipid-lowering therapies as well as the newly discovered therapies. For the classical therapies, we point out the importance of statins and ezetimibe in reducing plasma cholesterol levels by virtue of their effects on synthesis, reuptake and intestinal absorption of cholesterol. We also discuss the role of fibrates in modulating lipid metabolism and improving the ratio of high-density to low-density density lipoproteins. This study focuseson the more recent molecular and genetic interventions exemplified by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies, evinacumab, and microRNA inhibitors. Special attention is also given to clinical trials involving these therapies.
Subject(s)
Atherosclerosis , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Myocardial Infarction , Antibodies, Monoclonal/therapeutic use , Atherosclerosis/drug therapy , Cholesterol, LDL , Ezetimibe , Fibric Acids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Proprotein Convertase 9ABSTRACT
BACKGROUND: Liver diseases is a worldwide etiology causing high morbidity and mortality. Fibroscan is a quick, painless examination performed in clinic or at the patient's bedside. It is used to evaluate liver status for patients with suspected liver disease prognosis. This study aims at describing the spectrum of liver diseases among patients performing Fibroscan at a tertiary care center in Lebanon. METHODS: This is a retrospective data collection study on patients who underwent Fibroscan at the American University of Beirut hepatobiliary unit between 2015 and 2018. Medical charts of all patients were reviewed. Data were collected and analyzed using SPSS 25 software. RESULTS: A total of 620 patients presented to the hepatobiliary unit for Fibroscan, of which 419 (67.5%) were males. The mean age was 47.8 ± 13.4 (range 18-84). 362(58.3%) had NAFLD, 89 (14.3%) had Hepatitis-B, 69 (11.1%) had Hepatitis-C, 48 (7.7%) had ALD, 20 (3.3%) had DILI, and 13 (2.9%) had autoimmune hepatitis. 190 (30.6%) were overweight (BMI over 25), 128 (20.6%) had diabetes. Liver stiffness corresponding to the diagnosis of F4 liver fibrosis stage on Fibroscan was mostly reported in 6 (46.5%) autoimmune hepatitis, 101 (27.9%) NAFLD, and 18 (26.1%) HCV patients. 141 (45.5%) patients who had one or more metabolic risk factors suffered from severe stage steatosis compared with 78 (28.9%) who had not any risk factors with P-value 0.04. CONCLUSIONS: Based on our sample, NAFLD is emerging as a predominant etiology of CLD, followed by, HBV, and HCV. This is the first study that reports CLD status in Lebanon, further studies that describe the prevalence and incidence of the disease at a larger scale are needed.
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BACKGROUND & AIMS: Liver fibrosis is a metabolic disease associated with several factors, mainly age, gender, immune suppression, viral hepatitis, alcohol and metabolic diseases. Here, we are assessing the gender impact on liver status in NAFLD patients younger than 50 years. METHODS: All males younger than 50 years and premenopausal females diagnosed with NAFLD were included in this study. Fibroscan results, demographics and clinical data were collected and analyzed by SPSS software. Patients were stratified based on fibrosis scores as mild or no fibrosis for F0-F1-F2 and severe fibrosis for F3 and F4. Data was analyzed and compared based on gender. RESULTS: A total of 221 patients 134 males and 80 premenopausal females were included. Factors that affected liver fibrosis scores were different between males and females, where only body-mass index (BMI), white blood cells (WBC) count, and glucose level were associated with severe liver fibrosis in females. Also, liver fibrosis scores were associated with severe liver fibrosis in males only, no difference in these scores was observed in premenopausal females with severe or mild liver fibrosis. CONCLUSIONS: Gender differences are prominent in NAFLD and different factors are associated with liver status in males as compared to females. Besides, fibrosis score could predict liver status in males but not in females. Further larger-scale studies are necessary to verify gender impact on liver fibrosis development.