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Background: Dysphagia can involve any structure from the mouth to the lower esophageal sphincter. The etiologies vary from benign causes to malignant lesions. There is dearth of data regarding dysphagia in our population. Methods: A total of 208 patients with complaints of dysphagia were screened for the study. After ruling out neurological/local oropharyngeal causes of dysphagia, 200 patients with suspected esophageal dysphagia (ED) were recruited in the study. Dysphagia was graded as per the dysphagia scoring system. All patients underwent upper gastro-intestinal endoscopy and were evaluated for the presence of mechanical and non-mechanical causes of ED. Results: The mean age of patients with dysphagia was 53.8 ± 15.4 years. with males and females being 82 and 118, respectively. The mean duration of the symptom was 7.2 ± 10.6 months (median 3 months). Ninety-eight patients (49%) having dysphagia were in the age group of 56-65 years. The dysphagia score was 0 among 58, and 4 among 26 subjects. Foreign body sensation was the most frequent chief complaint in 90 (45%) patients. Ninety-six (48%) and 104 (52%) patients had mechanical and non-mechanical causes of dysphagia, respectively. Among mechanical causes of dysphagia, 68 patients (70.8%) had esophageal growth and 28 (29.2%) had esophageal stricture. Sixty-seven patients had squamous cell carcinoma. Among non-mechanical causes, 50 (48.1%) had globus sensation, 24 (23.1%) had hiatus hernia, and 16 (15.4%) functional dysphagia. Conclusion: Dysphagia is a common problem with varied etiologies. The esophageal growth and globus sensation are among the predominant causes of ED. We stress that all patients of dysphagia must be meticulously investigated.
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AIM: Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored till date. METHODS: Human gut microbiota composition and meta-gut resistome was evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to get insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. RESULTS: In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy control (HC) [518]. Metagenome study revealed higher prevalence of AMR genes in rural population (378 in HC; 607 in UC) compared to urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and immuneproteins (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. CONCLUSIONS: In addition to the conventional culturomics method, multi-omics strategy provides deeper insights into the disease etiology, emergence of pathobionts, andits role in the disruption of the healthy gut environment in UC patients.
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BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.
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BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.
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Apéndice Atrial , Fibrilación Atrial , Cateterismo Cardíaco , Remoción de Dispositivos , Sistema de Registros , Humanos , Masculino , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Femenino , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Tiempo , Anciano de 80 o más Años , Factores de Riesgo , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/mortalidad , Fibrilación Atrial/terapia , Fibrilación Atrial/mortalidad , Remoción de Dispositivos/efectos adversos , Embolia/etiología , Embolia/mortalidad , Persona de Mediana Edad , Dispositivo Oclusor Septal , Cierre del Apéndice Auricular IzquierdoRESUMEN
INTRODUCTION: Percutaneous left atrial appendage occlusion (LAAO) is traditionally performed under general anesthesia with trans-esophageal echocardiography guidance. Intracardiac echo (ICE)-guided LAAO closure is increasing in clinical use. The ICE catheter is crossed into LA via interatrial septum (IAS) after the septum is dilated with LAAO delivery sheath. This step can be time-consuming and requires significant ICE catheter manipulation, which increases the risk of cardiac perforation. Pre-emptive septal balloon dilation can potentially help with ICE advancement in the LA. We sought to evaluate the effect of pre-dilation of the IAS with an 8 mm balloon on the ease of crossing the ICE catheter, fluoroscopy time for crossing, and overall procedure time. METHODS: The Piedmont LAAO registry was used to identify consecutive patients who underwent LAAO. The initial 25 patients in whom balloon dilation of the IAS was performed served as the experimental cohort, and the 25 consecutive patients before that in whom balloon dilation was not performed served as controls. In the experimental group, after a trans-septal puncture, the sheath was retracted to the right atrium with a guidewire still in the LA. An 8 × 40 mm Evercoss™ over the wire balloon was inflated across the IAS. The ICE catheter was then crossed into the LA using the fluoroscopic landmark of the guide wire and the ICE imaging. The sheath was then advanced along the ICE catheter via the transseptal puncture (TSP) and the procedure continued. Follow-up compputed tomography imaging was obtained at 4-8 weeks. RESULTS: Each group consisted of 25 patients. There were no significant differences in baseline characteristics. All procedures were performed successfully under conscious sedation and ICE guidance. There was a significant reduction in the overall procedure time, fluoroscopy time, and time for transseptal puncture to ICE in LA. There was no difference in the size of the acute residual interatrial shunt, as measured via ICE, or the size and presence of iatrogenic ASD at follow-up. CONCLUSION: Balloon dilation of TSP is safe and is associated with increased efficiency in ICE-guided LAAO procedures.
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Apéndice Atrial , Fibrilación Atrial , Cateterismo Cardíaco , Sistema de Registros , Humanos , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/fisiopatología , Masculino , Femenino , Anciano , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/efectos adversos , Resultado del Tratamiento , Fibrilación Atrial/terapia , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Ultrasonografía Intervencional , Factores de Tiempo , Anciano de 80 o más Años , Persona de Mediana Edad , Tabique Interatrial/diagnóstico por imagen , Valor Predictivo de las PruebasRESUMEN
INTRODUCTION: During atrial fibrillation ablation (AFA), achievement of first pass isolation (FPI) reflects effective lesion formation and predicts long-term freedom from arrhythmia recurrence. We aim to determine the clinical and procedural predictors of pulmonary vein FPI. METHODS: We reviewed AFA procedures in a multicenter prospective registry of AFA (REAL-AF). A multivariate ordinal logistic regression, weighted by inverse proceduralist volume, was used to determine predictors of FPI. RESULTS: A total of 2671 patients were included with 1806 achieving FPI in both vein sides, 702 achieving FPI in one, and 163 having no FPI. Individually, age, left atrial (LA) scar, higher power usage (50 W), greater posterior contact force, ablation index >350 posteriorly, Vizigo™ sheath utilization, nonstandard ventilation, and high operator volume (>6 monthly cases) were all related to improved odds of FPI. Conversely sleep apnea, elevated body mass index (BMI), diabetes mellitus, LA enlargement, antiarrhythmic drug use, and center's higher fluoroscopy use were related to reduced odds of FPI. Multivariate analysis showed that BMI > 30 (OR 0.78 [0.64-0.96]) and LA volume (OR per mL increase = 1.00 [0.99-1.00]) predicted lower odds of achieving FPI, whereas significant left atrial scarring (>20%) was related to higher rates of FPI. Procedurally, the use of high power (50 W) (OR 1.32 [1.05-1.65]), increasing force posteriorly (OR 2.03 [1.19-3.46]), and nonstandard ventilation (OR 1.26 [1.00-1.59]) predicted higher FPI rates. At a site level, high procedural volume (OR 1.89 [1.48-2.41]) and low fluoroscopy centers (OR 0.72 [0.61-0.84]) had higher rates of FPI. CONCLUSION: FPI rates are affected by operator experience, patient comorbidities, and procedural strategies. These factors may be postulated to impact acute lesion formation.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Venas Pulmonares/cirugía , Resultado del Tratamiento , Estudios Prospectivos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Atrios Cardíacos , Cicatriz , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Recurrencia , Estudios Multicéntricos como AsuntoRESUMEN
Atrial fibrillation (AF) and heart failure are common overlapping cardiovascular disorders. Despite important therapeutic advances over the past several decades, controversy persists about whether a rate control or rhythm control approach constitutes the best option in this population. There is also considerable debate about whether antiarrhythmic drug therapy or ablation is the best approach when rhythm control is pursued. A brief historical examination of the literature addressing this issue will be performed. An analysis of several important clinical outcomes observed in the prospective, randomized studies, which have compared AF ablation to non-ablation treatment options, will be discussed. This review will conclude with recommendations to guide clinicians on the status of AF ablation as a treatment option when considering management options in heart failure patients with atrial fibrillation.
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Fibrilación Atrial , Ablación por Catéter , Insuficiencia Cardíaca , Humanos , Estudios Prospectivos , Antiarrítmicos/uso terapéutico , Insuficiencia Cardíaca/terapia , Pacientes , Resultado del TratamientoRESUMEN
BACKGROUND: High-power short-duration (HPSD) radiofrequency ablation of atrial fibrillation (AF) increases first-pass pulmonary vein isolation (PVI) and freedom from atrial arrhythmias while decreasing procedural time. However, the optimal power setting in terms of safety and efficacy has not been determined. OBJECTIVES: This study compared the procedural characteristics and clinical outcomes of 50-W vs 40-W during HPSD ablation of paroxysmal AF. METHODS: Patients from the REAL-AF prospective multicenter registry (Real-World Experience of Catheter Ablation for Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation) undergoing HPSD ablation of paroxysmal AF, either using 50-W or 40-W, were included. The primary efficacy outcome was freedom from all-atrial arrhythmias. The primary safety outcome was the occurrence of any procedural complication at 12 months. Secondary outcomes included procedural characteristics, AF-related symptoms, and the occurrence of transient ischemic attack or stroke at 12 months. RESULTS: A total of 383 patients were included. Freedom from all-atrial arrhythmias at 12 months was 80.7% in the 50-W group and 77.3% in the 40-W group (Log-rank P = 0.387). The primary safety outcome occurred in 3.7% of patients in the 50-W group vs 2.8% in the 40-W group (P = 0.646). The 50-W group had a higher rate of first-pass PVI (82.3% vs 76.2%; P = 0.040) as well as shorter procedural (67 minutes [IQR: 54-87.5 minutes] vs 93 minutes [IQR: 80.5-111 minutes]; P < 0.001) and radiofrequency ablation times (15 minutes [IQR: 11.4-20 minutes] vs 27 minutes [IQR: 21.5-34.6 minutes]; P < 0.001) than the 40-W group. CONCLUSIONS: There was no significant difference in freedom from all-atrial arrhythmias or procedural safety outcomes between 50-W and 40-W during HPSD ablation of paroxysmal AF. The use of 50-W was associated with a higher rate of first-pass PVI as well as shorter procedural times.
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Fibrilación Atrial , Ablación por Catéter , Criocirugía , Humanos , Estudios Prospectivos , Recurrencia Local de Neoplasia/etiología , Factores de Tiempo , Ablación por Catéter/efectos adversosRESUMEN
The highly biocompatible nature of carbon dots (CQDs) and potential usage in waste water treatment makes them as one of the effective alternative for treating water pollution. Herein, biogenic carbon dots (CQDs) with size range of 2 nm were prepared from waste coconut husk as a precursor source. The hydrophilic nature and higher surface area of as prepared CQDs has further supported the superior adsorption efficiency of more than 90% for Victoria blue B (VB) dye from waste water samples. Different dye adsorption parameters including adsorbate and adsorbent dosage, pH of reaction media and equilibrium time have been optimized and found that 8 mg of adsorbent was sufficient to remove 70 mg VB dye in 4 mL aqueous solution in 60 min at pH = 7. The adsorption kinetic (2nd order) and isotherms (Freundlich-type) were well followed on prepared CQDs. The reusability studies up to 5 times with minimal decrement of 4% confirm the constancy of CQDs for the adsorptive removal of VB. The methodology presents a greener way for overcoming ecological issues with sustainable materials in an economical manner.
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Carbono , Contaminantes Químicos del Agua , Cocos , Colorantes de Rosanilina , Adsorción , Cinética , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND: Health Care workers (HCWs) have an approximate four-fold increased risk of contracting hepatitis B infection than the normal population. A lack of knowledge and practices regarding precautions has been frequently observed. We aimed to do a knowledge, attitude, and practices (KAP) study regarding hepatitis B prevention measures among HCWs. METHODS: The study enrolled 250 HCWs. A questionnaire-based proforma regarding KAP towards hepatitis B, its causation, and prevention was filled out by each participant. RESULTS: Mean age (SD) of participants was 31.8 ± 9.1 years with 83 males and 167 females. Subjects were divided into two groups: Group I (House Surgeons and Residents) and Group II (Nursing staff, Laboratory Technicians, Operation Theatre Assistants). All Group I and 148 (96.7%) of Group II subjects had adequate knowledge regarding the professional risk of hepatitis B virus transmission. Knowledge regarding different modes of transmission was less in Group II subjects (Blood (96.1%), Sex (84.3%), percutaneous route (85.6%), and During Birth (83%)) as compared to Group I (100% in all). All subjects in Group I and 134 (90.9%) Group II subjects knew about vaccination as a preventive measure. There was a slight discordance between attitude and practices towards universal precautionary measures in Group II subjects (Use of gloves 96.1% vs 94.8%; Safe needle disposal 96.7% vs 96.1%; Vaccination 94.8% vs 67.9%). Of the subjects in Group I, 94.8% were vaccinated and 67.9% were vaccinated in Group II, with complete vaccination rates being 76.3% and 43.1%, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Better knowledge and attitude led to more adoption of preventive practices. But, still, there is a gap in the KAP towards hepatitis B preventive practices and knowledge is not getting transformed into practices. We recommend that all HCWs should be questioned about their vaccination status. In addition, vaccination coverage, various preventive campaigns, and the hospital infection control committee (HICC) need to be strengthened.
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Ranking from seventh in incidence to sixth in mortality, esophageal carcinoma is considered a severe malignancy of food pipe. Later-stage diagnosis, drug resistance, and a high mortality rate contribute to its lethality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two main histological subtypes of esophageal carcinoma, with squamous cell carcinoma alone accounting for more than eighty percent of its cases. While genetic anomalies are well known in esophageal cancer, accountability of epigenetic deregulations is also being explored for the recent two decades. DNA methylation, histone modifications, and functional non-coding RNAs are the crucial epigenetic players involved in the modulation of different malignancies, including esophageal carcinoma. Targeting these epigenetic aberrations will provide new insights into the development of biomarker tools for risk stratification, early diagnosis, and effective therapeutic intervention. This review discusses different epigenetic alterations, emphasizing the most significant developments in esophageal cancer epigenetics and their potential implication for the detection, prognosis, and treatment of esophageal carcinoma. Further, the preclinical and clinical status of various epigenetic drugs has also been reviewed.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Epigénesis Genética/genética , Metilación de ADN/genéticaRESUMEN
BACKGROUND: Same-day discharge (SDD) after catheter ablation of atrial fibrillation (AF) has been widely adopted. Nevertheless, planned SDD has been performed by using subjective criteria rather than standardized protocols. OBJECTIVES: The goal of this study was to determine the efficacy and safety of the previously described SDD protocol in a prospective multicenter study. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Paroxysmal and Persistent Atrial Fibrillation) SDD protocol eligibility criteria (stable anticoagulation, no bleeding history, left ventricular ejection fraction >40%, no pulmonary disease, no procedures within 60 days, and body mass index <35 kg/m2), operators prospectively determined whether patients undergoing ablation of AF were candidates for SDD (SDD vs non-SDD groups). Successful SDD was achieved if the patient met the protocol discharge criteria. The primary efficacy endpoint was the success rate of SDD. The primary safety endpoints were readmission rates as well as acute and subacute complications. The secondary endpoints included procedural characteristics and freedom from all-atrial arrhythmias. RESULTS: A total of 2,332 patients were included. The REAL-AF SDD protocol identified 1,982 (85%) patients as potential candidates for SDD. The primary efficacy endpoint was achieved in 1,707 (86.1%) patients. The readmission rate for SDD vs non-SDD group was similar (0.8% vs 0.9%; P = 0.924). The SDD group had a lower acute complication rate than the non-SDD group (0.8% vs 2.9%; P < 0.001), and there was no difference in the subacute complication rate between groups (P = 0.513). Freedom from all-atrial arrhythmias was comparable between groups (P = 0.212). CONCLUSIONS: In this large, multicenter prospective registry, the use of a standardized protocol showed the safety of SDD after catheter ablation of paroxysmal and persistent AF. (Real-world Experience of Catheter Ablation for the Treatment of Paroxysmal and Persistent Atrial Fibrillation [REAL-AF]; NCT04088071).
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Fibrilación Atrial , Ablación por Catéter , Humanos , Alta del Paciente , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
BACKGROUND/AIMS: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. RESULTS: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. CONCLUSIONS: Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.
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Percutaneous left atrial appendage occlusion (LAAO) is contraindicated in presence of left atrial appendage (LAA) thrombus. It is often difficult to separate LAA sludge from an organized thrombus on transesophageal echocardiography. The inability to differentiate sludge from thrombus leads to patients not receiving LAAO despite contraindication to long-term anticoagulation. Retrospective 6-month follow-up outcomes are reported on patients undergoing LAAO in presence of LAA sludge cleared by isoproterenol. This study showed no increased risk of transient ischemic attack/stroke in the 6 months following LAAO in the presence of LAA sludge, which was cleared with isoproterenol. This study suggests a role for isoproterenol in differentiating sludge from thrombus.
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Apéndice Atrial , Fibrilación Atrial , Cardiopatías , Trombosis , Humanos , Isoproterenol/uso terapéutico , Aguas del Alcantarillado , Apéndice Atrial/diagnóstico por imagen , Apéndice Atrial/cirugía , Estudios Retrospectivos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/cirugía , Trombosis/etiología , Cardiopatías/etiologíaRESUMEN
Aim of the study: Despite having ample literature in hepatorenal syndrome-acute kidney injury (HRS-AKI) in decompensated cirrhosis patients, there is a scarcity of data on acute-on-chronic liver failure-acute kidney injury (ACLF-AKI). We compared terlipressin infusion with bolus in ACLF-AKI patients. Material and methods: Patients with ACLF (as per the CANONIC study) were screened for AKI as per the 2015 ICA-AKI criteria. If after 48 h of volume expansion with albumin, serum creatinine (sCr) did not improve, patients were randomized into two groups: Terli-infusion (Terli-I) 2 mg/day and Terli-bolus (Terli-B) 1 mg q6h. If sCr did not decrease < 25% of pretreatment value after 48 h, the terlipressin dose was increased to a maximum of 12 mg/day. The primary outcome was taken as regression (full or partial response), stable/no response and progression of AKI to higher stages and secondary outcomes were taken as 28-day and 90-day mortality. Results: After screening 136 patients with ACLF-AKI, Terli-I (n = 50) and Terli-B (n = 50) with mean sCr 2.4 and 2.1 mg/dl respectively were enrolled. The regression of AKI (full response 37 vs. 27, partial response 3 vs. 9, p = 0.5), stable (2 vs. 5, p = 0.6), progression of AKI (8 vs. 7, p = 0.2) were present in Terli-I and Terli-B respectively. No significant difference was found in 28-and 90-day mortality. In Terli-B, mean terlipressin dose was 8 vs. 4 mg, p < 0.008 with more side effects, 15 vs. 0, p < 0.01 than Terli-I respectively. Conclusions: Terlipressin infusion is more effective than bolus doses in regression of acute kidney injury and better tolerated in acute-on-chronic liver failure-AKI patients.
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Cyclic GMP-AMP synthase (cGAS) is an endogenous DNA sensor that synthesizes cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) from ATP and GTP. 2'3'-cGAMP activates the stimulator of interferon genes (STING) pathway, resulting in the production of interferons and pro-inflammatory cytokines. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the phosphodiesterase that negatively regulates the STING pathway by hydrolyzing 2'3'-cGAMP. It has been established that the cGAS-STING pathway plays a major role in inhibiting tumor growth by upregulating T cell response. Herein, we demonstrate that AVA-NP-695, a selective and highly potent ENPP1 inhibitor, apart from the immunomodulatory effect also modulates cancer metastasis by negatively regulating epithelial-mesenchymal transition (EMT). We established that the combined addition of 2'3'-cGAMP and AVA-NP-695 significantly abrogated the transforming growth factor beta (TGF-êµ)-induced EMT in MDA-MB-231 cells. Finally, results from the in vivo study showed superior tumor growth inhibition and impact on tumor metastasis of AVA-NP-695 compared to Olaparib and PD-1 in a syngeneic 4T1 breast cancer mouse model. The translation of efficacy from in vitro to in vivo 4T1 tumor model provides a strong rationale for the therapeutic potential of AVA-NP-695 against triple-negative breast cancer (TNBC) as an immunomodulatory and anti-metastatic agent.
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Receptor de Muerte Celular Programada 1 , Neoplasias de la Mama Triple Negativas , Adenosina Trifosfato/metabolismo , Animales , ADN , Guanosina Trifosfato , Humanos , Interferones , Proteínas de la Membrana/metabolismo , Ratones , Nucleotidiltransferasas/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Pirofosfatasas/metabolismo , Factor de Crecimiento Transformador betaRESUMEN
Background: Literature suggests that the COVID-19 pandemic has resulted in poor sleep quality, especially among the infected population. However, literature regarding the effect of COVID-19 pandemic and SARS-CoV-2 infection on occurrence of insomnia, restless legs syndrome and dream enactment behavior is either scarce or unavailable. Methods: This study was planned to assess the effect of SARS-CoV-2 infection on the occurrence of insomnia, restless legs syndrome (RLS) and dream enactment behavior (DEB). For this cross-sectional study, a questionnaire comprising of items related to demographic details, past medical history, and information related to SARS-CoV-2 infection was distributed through social media. Insomnia was diagnosed using clinical criteria. RLS, DEB, sleep quality, depression and anxiety were assessed using a validated questionnaire. Information regarding the use of hypnotic medications was also gathered. Results: Of the 1596 respondents, 37.2% reported disturbed sleep while insomnia was reported by 22.6% respondents. 27.3% of respondents reported RLS and 17.4% suffered DEB. The odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03-1.58; P < 0.02) and among those who had SARS-CoV-2 infection (OR = 1.76; 95% CI = 1.42-2.19; P < 0.001). Similarly, SARS-CoV-2 infection was also associated with increased odds of RLS (OR = 2.48; 95% CI = 1.98-3.11; P < 0.001) and DEB (OR = 1.58; 95%CI = 1.21-2.06; P < 0.001). Insomnia, RLS and DEB were more frequent among respondents who required oxygen therapy, those who experienced loss of taste and/or smell, depression and anxiety. Prevalence of insomnia, DEB and RLS was higher than said prevalence among respondents with no history of SARS-CoV-2 infection, but lower than that of those with positive history of SARS-CoV-2 infection. 5.3% of respondents reported taking hypnotic medications before infection, 7% during infection and 5.3% after infection. Conclusion: SARS-CoV-2-infection-related factors in association with environmental factors have increased the prevalence of insomnia, DEB and RLS among subjects having infection. SARS-CoV-2-associated immunological changes, hypoxia and neurotropism may play a role in occurrence of insomnia, DEB and RLS.
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BACKGROUND: In natural history of cirrhosis, variceal bleeding is one of the earliest decompensations to happen, and, if adequately managed, survival is improved. Gastric varices have challenges in management due to their location, size and propensity to bleed. The N-butyl 2-cyanoacrylate (NBC) glue application has emerged as definitive therapy in bleeding gastric varices. Here we present our experience with use of NBC in management of gastric and difficult cases of esophageal varices. METHODS: A total of 75 patients underwent NBC glue application for varices which included 69 patients with gastric varices and six patients with esophageal varices. All the procedures were done with flexible endoscope and sclerotherapy needle after due precautionary measures. RESULTS: Hemostasis was varices in all patients after endotherapy. The average quantity of glue used was 2.75±0.95 mL. Complete obliteration with single session of NBC application was achieved in 55 patients. Re-bleeding occurred in five patients within 5 days of index event. 20 patients had in-hospital mortality but none was related to gastrointestinal bleeding. 6-week all-cause mortality was 26 (35%). CONCLUSION: Glue therapy with NBC is a life saving therapy in patients with bleeding gastric varices and esophageal varices not amenable to endoscopic variceal ligation or sclerotherapy.
Asunto(s)
Enbucrilato , Várices Esofágicas y Gástricas , Várices , Cianoacrilatos/uso terapéutico , Enbucrilato/uso terapéutico , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Humanos , India , Resultado del Tratamiento , Várices/complicacionesRESUMEN
ABSTRACT Background: In natural history of cirrhosis, variceal bleeding is one of the earliest decompensations to happen, and, if adequately managed, survival is improved. Gastric varices have challenges in management due to their location, size and propensity to bleed. The N-butyl 2-cyanoacrylate (NBC) glue application has emerged as definitive therapy in bleeding gastric varices. Here we present our experience with use of NBC in management of gastric and difficult cases of esophageal varices. Methods: A total of 75 patients underwent NBC glue application for varices which included 69 patients with gastric varices and six patients with esophageal varices. All the procedures were done with flexible endoscope and sclerotherapy needle after due precautionary measures. Results: Hemostasis was varices in all patients after endotherapy. The average quantity of glue used was 2.75±0.95 mL. Complete obliteration with single session of NBC application was achieved in 55 patients. Re-bleeding occurred in five patients within 5 days of index event. 20 patients had in-hospital mortality but none was related to gastrointestinal bleeding. 6-week all-cause mortality was 26 (35%). Conclusion: Glue therapy with NBC is a life saving therapy in patients with bleeding gastric varices and esophageal varices not amenable to endoscopic variceal ligation or sclerotherapy.
RESUMO Contexto: Na história natural da cirrose, o sangramento de varizes é uma das primeiras descompensações a acontecer e, se adequadamente controlada, a sobrevivência é melhorada. Varizes gástricas têm desafios na sua gestão devido à sua localização, tamanho e propensão a sangrar. A aplicação de cola N butil 2-cianoacrilato (NBC) surgiu como terapia definitiva em varizes gástricas sangrantes. Apresentamos nossa experiência com o uso da NBC na gestão de casos gástricos e difíceis de varizes esofágicas. Métodos: Um total de 75 pacientes foram submetidos à aplicação de cola NBC para varizes que incluiu 69 pacientes com varizes gástricas e seis pacientes com varizes de esôfago. Todos os procedimentos foram feitos com endoscópio flexível e agulha de escleroterapia após as devidas medidas de precaução. Resultados: A hemostasia foi alcançada em todos os pacientes após a endoterapia. A quantidade média de cola utilizada foi de 2,75+0,95 mL. A obliteração completa com sessão única de aplicação da NBC foi alcançada em 55 pacientes. O reexame ocorreu em cinco pacientes dentro de 5 dias após o evento de índice. 20 pacientes tiveram mortalidade hospitalar, mas nenhum foi relacionado com o sangramento gastrointestinal. A mortalidade após 6 semanas foi de 26 (35%). Conclusão: A terapia de cola com a NBC é uma terapia que salva vidas em pacientes com varizes gástricas hemorrágicas e varizes esofágicas não condizíveis à ligadura endoscópica ou escleroterapia.
RESUMEN
BACKGROUND: Acute kidney injury (AKI) in cirrhosis is important complication with poor outcomes. And infections are common cause for acute decompensation. Infections in cirrhosis lead to acute deterioration of hemodynamics leading to precipitation of AKI. AIM: To study predictors of mortality in patients with infection-associated AKI in cirrhosis. METHODS: This was a prospective, observational study conducted at tertiary care centre from January 2018 till April 2019. Total 119 participants with cirrhosis of liver presenting with AKI were included into the study. AKI was defined as per international club of Ascites-AKI criteria 2015. Patients were grouped into infection AKI and non-infection AKI. Non-infection AKI included patients with diuretic induced AKI and pre-renal AKI. Logistic regression analysis was used to determine predictors of mortality at 28-d. RESULTS: Out of 119 patients, alcohol (n = 104) was most common etiology of cirrhosis. The infection AKI included 67 (56%) patients and non-infection AKI (n = 52) included pre-renal AKI in 36 (30%) and diuretic-induced AKI in 16 (14%) patients. Infection AKI had significantly higher bilirubin, higher international normalized ratio (INR), low serum sodium, higher total leukocyte count (TLC) and higher prevalence of hepatic encephalopathy (HE) as compared to non-infection AKI. Infection AKI had higher progression of AKI (19/67 vs 2/52; P = 0.01) and 28-d mortality (38/67 vs 4/5; P ≤ 0.01) as compared to non-infection AKI. At 28-d, non-survivors (n = 42) had significantly higher bilirubin, higher INR, low serum sodium, higher TLC and higher prevalence of HE as compared to survivors (n = 77). On subgroup analysis of Infection AKI group, on multivariate analysis, serum bilirubin as well as presence of HE were independent predictors of 28-d mortality. There was no significant difference of mortality at 90-d between two groups. CONCLUSION: Infection AKI in cirrhosis has a dismal prognosis with higher 28-d mortality as compared to non-infection AKI. Serum bilirubin and presence of HE predict 28-d mortality in infection AKI.