Pathogenesis of chronic rhinosinusitis with nasal polyp and a prominent T2 endotype.

Chronic rhinosinusitis is a heterogenous and multifactorial disease, characterized by persistent inflammation of the nose and paranasal sinuses, which causes nasal obstruction, nasal discharge, facial pain, and smell disturbance. Chronic rhinosinusitis is divided into two phenotypes: chronic rhinosinusitis with nasal polyp and chronic rhinosinusitis without nasal polyp. Nasal polyps can be associated with many inflammatory cells including eosinophil cells, neutrophil cells, plasma cells, and lymphocytes. T2 endotype is characterized by the type-2 immune response and nasal polyps are associated with eosinophilic dominant infiltration. In contrast, in the T1 and T3 endotypes, chronic rhinosinusitis can be associated with neutrophilic dominant infiltration. In addition, there are mixed types of inflammation with different proportions of eosinophils-neutrophils in chronic rhinosinusitis. In the T2 endotype, there is an increase in the production of Th2 cytokines, including interleukin-4, interleukin-5, and interleukin-13, high levels of immunoglobulin-E in polyp tissue, and eosinophilia. Stimulation of Th2 cells, type-2 innate lymphoid cells, epithelial cell damage, Staphylococcus aureus enterotoxins, and autoimmune antibodies have important roles in the enhancement of Th2 cytokines and pathogenesis of chronic rhinosinusitis with nasal polyp. Monoclonal antibodies target type-2 inflammation, decrease nasal polyp size, and improve the clinical symptoms of CRSwNP patients. The present review will focus on factors involved in the pathogenesis of chronic rhinosinusitis and its treatment.

The attitude and knowledge of pediatricians and family physicians toward COVID-19 vaccination in children: A cross-sectional study.

COVID-19 vaccines to children are expected to reduce the transmission of the disease to high-risk groups and achieve herd immunity in younger populations. A positive attitude toward COVID-19 vaccination in children among healthcare workers (HCWs) is predicted to reduce parents' hesitancy to vaccinate their children. This study aimed to assess the knowledge and attitude of pediatricians and family physicians toward COVID-19 vaccination in children. A total of 112 pediatricians and 96 family physicians (specialists and residents) were interviewed to assess the level of knowledge, attitude, and perceived safety of COVID-19 vaccines for children. Physicians willing to receive regular COVID-19 vaccination (analogous to the influenza vaccine) had significantly higher knowledge and attitude scores (P < .05). Multivariate analysis indicated that a higher knowledge score and having at least five years of experience as a specialist were significantly associated with a positive attitude among pediatricians or family physicians (P < .05). Pfizer/BioNTech was the preferred COVID-19 vaccine in children among physicians of both groups (>67%). Around 71% of physicians believed COVID-19 vaccines for children do not cause or worsen any health condition. Educational and training programs that increase the knowledge of physicians about COVID-19 vaccines and their safety in children are recommended to inform a more positive attitude.

Hemofiltration as an Alternative for IL-6 Inhibitors in COVID-19 Cytokines Storm Associated with Underlaying Bacterial Infections: A Review Article.

SARS-CoV-2 causes mostly mild cases. However, a considerable number of patients develop fatal acute respiratory distress syndrome due to the cytokine storm and imbalanced immune response. Several therapies depending on immunomodulation have been used, including glucocorticoids and IL-6 blockers. However, their efficacy is not perfect with all patients and patients with concomitant bacterial infections and sepsis. Accordingly, studies on different immunomodulators, including extracorporeal techniques, are crucial to save this category of patients. In this review, we overviewed the different immunomodulation techniques shortly, with a brief review of extracorporeal methods.

Ethnic Differences in Clinical Presentations and Esophageal High-Resolution Manometry Findings in Patients with Achalasia.

BACKGROUND: Ethnic differences in achalasia presentations have scarcely been described. The association between achalasia and immunologic HLA haplotypes suggests that there may be a genetic predisposition. We aimed to evaluate differences in demographic, clinical, endoscopic, and manometric findings between two distinct ethnic groups with achalasia-Israeli Arabs (IA) and Israeli Jews (IJ). METHODS: A retrospective study was performed at two medical centers. High-resolution manometry (HRM) reports were reviewed for newly-diagnosed achalasia patients. Demographic data, clinical presentations, endoscopy reports, and HRM metrics including the integrated relaxation pressure (IRP) were all reviewed. RESULTS: Overall, 94 achalasia patients were included (53.2% male; mean age 54.5 ± 18.0). 43 patients were IA (45.7%). Body mass index (BMI) was similar in both groups. Compared to IJ, the IA patients had more esophageal dysphagia (100% vs. 88.2%; P = 0.022), chest pain (46.5% vs. 25.5%; P = 0.033), and a tortuous esophagus on endoscopy (23.3% vs. 3.9%; p = 0.005). IA patients were also diagnosed at a younger age than IJ patients (50.9 ± 17.5 vs. 57.5 ± 18.0; p = 0.039). Furthermore, IRP values were higher among IA patients than IJ patients (32.2 ± 13.8 vs. 23.3 ± 8.4; p < 0.001). A regression model analysis found that ethnicity significantly predicted IRP (ß = - 10, p < .001). CONCLUSION: Ethnicity appears to affect achalasia clinical presentation and HRM findings. IA achalasia patients are diagnosed at a younger age, present with more severe esophageal symptoms, and have a higher IRP compared to IJ patients. Additional studies of diverse, multiethnic populations, especially with genetic evaluations, are required to further assess the role of ethnicity in achalasia.

The possible association of proton pump inhibitor use with acute cholangitis in patients with choledocholithiasis: a multi-center study.

BACKGROUND: Gallstone disease is common worldwide and can lead to severe complications, including cholangitis; thus, it is important to identify modifiable risk factors for cholangitis. Proton pump inhibitors (PPIs) are commonly prescribed to treat gastroenterological disorders. We aimed to explore whether PPI use is associated with an increased risk of acute cholangitis in patients with gallstone disease. METHODS: This retrospective multicenter study included all patients arriving to the hospital over a 10-year period with various presentations of choledocholithiasis. We compared active PPI use in two groups: those with cholangitis (group A) vs. without cholangitis (group B). RESULTS: Overall, 811 patients were included, 161 in group A and 650 in group B. The average age ± standard deviation (SD) in groups A and B was 74.5 ± 20.6 vs. 61.6 ± 20.9 years, respectively. PPI use in group A was higher vs. group B (42.9% vs. 29.1%, p = 0.001). On univariate analysis, male gender (OR 1.47, 95% confidence interval (CI) 1.04-2.08), age (OR 1.04, 95% CI 1.03-1.05), ischemic heart disease (IHD) (OR 1.68, 95% CI 1.07-2.64), hyperlipidemia (OR 1.59, 95% CI 1.11-2.29), hypertension (OR 1.81, 95% CI 1.28-2.57) and PPI use (OR 1.83, 95% CI 1.28-2.61), all were associated with acute cholangitis. On multivariate analysis, only PPI use kept its association after adjustment for age (OR 1.64, 95% CI 1.2-3.7). CONCLUSIONS: Active PPI use was associated with a higher rate of cholangitis among patients with choledocholithiasis. We advocate considering this risk before prescribing PPIs to patients with gallstones. TRIAL REGISTRATION NUMBER: NHR-0263-20 received on 14/01/2021 date 'retrospectively registered'.

The yield of solid swallows in high resolution esophageal manometry among patients with dysphagia and gastro-esophageal reflux symptoms.

BACKGROUND: Swallowing disorders are frequently reported esophageal symptoms and represent a common cause for referrals to gastroenterology consultations. Esophageal high-resolution manometry (HRM) is considered the gold standard modality for the evaluation of esophageal peristalsis and esophageal sphincter. The standard protocol of HRM includes water swallows only, that may not assess appropriately esophageal function and symptoms. Hence, we investigated the diagnostic yield of combining solid food swallows (SFS) to standard HRM. METHODS: We conducted a retrospective study at the Gastroenterology unit of EMMS Nazareth Hospital, Israel. Patients who underwent manometry mainly due to dysphagia or reflux symptoms between November 2019 and November 2020 were enrolled. All patients underwent routine HRM and completed ten 5 ml water swallows and 5 bread swallows. Analysis and reports were done by an expert gastroenterologist, based on the Chicago Classification version 3. RESULTS: Overall, 99 patients (45.5% men, mean age 52.1±16 years) who underwent HRM were included. The addition of solid swallows to the test changed manometry results in 43 patients (43.4%) (P<0.005). Furthermore, SFS improved the contractility in 26/42 cases of ineffective and/or absent motility (61%) (P< 0.005). Finally, SFS aggravated symptoms in 44 patients (44.6% more aggravation than in liquid only) (P<0.005). CONCLUSIONS: Combining SFS to HRM can improve the diagnostic yield of the study. Adding solid swallows is of special value in cases of ineffective esophageal motility but induces a high rate of symptoms aggravation.

Adaption of distance learning to continue the academic year amid COVID-19 lockdown.

This work investigates the use of distance learning in saving students' academic year amid COVID-19 lockdown. It assesses the adoption of distance learning using various online application tools that have gained widespread attention during the coronavirus infectious disease 2019 (COVID-19) pandemic. Distance learning thrives as a legitimate alternative to classroom instructions, as major cities around the globe are locked down amid the COVID-19 pandemic. To save the academic year, educational institutions have reacted to the situation impulsively and adopted distance learning platforms using online resources. This study surveyed random undergraduate students to identify the impact of trust in formal and informal information sources, awareness and the readiness to adopt distance learning. In this study, we have hypothesized that adopting distance learning is an outcome of situational awareness and readiness, which is achieved by the trust in the information sources related to distance learning. The findings indicate that trust in information sources such as institute and media information or interpersonal communication related to distance learning programs is correlated with awareness (ß = 0.423, t = 12.296, p = 0.000) and contribute to readiness (ß = 0.593, t = 28.762, p = 0.001). The structural model path coefficient indicates that readiness strongly influences the adoption of distance learning (ß = 0.660, t = 12.798, p = 0.000) amid the COVID-19 pandemic. Our proposed model recorded a predictive relevance (Q2) of 0.377 for awareness, 0.559 for readiness, and 0.309 for the adoption of distance learning, which explains how well the model and its parameter estimates reconstruct the values. This study concludes with implications for further research in this area.

The Yield of Endoscopy and Histology in the Evaluation of Esophageal Dysphagia: Two Referral Centers' Experiences.

Background and Objectives: The initial diagnostic test required to evaluate esophageal dysphagia is upper endoscopy (EGD) to assess the structure of the esophagus and the esophageo-gastric junction (EGJ). Taking biopsies during EGD has become a common practice in patients with dysphagia to rule out eosinophilic esophagitis (EoE). The aims of this study were to evaluate the endoscopic findings of patients who underwent EGD for esophageal dysphagia, to assess the rate of biopsy taking from the esophagus to diagnose/exclude EoE, and to report histology outcomes of these biopsies. Materials and Methods: This was a retrospective multicenter study that included individuals ≥18 years who underwent EGD due to esophageal dysphagia between the years 2015 and2020, (with no other alarm signs, such as weight loss, new iron deficiency anemia, and lymphadenopathy). We obtained data from patients' electronic files. The endoscopy and histology findings were obtained from endoscopy reports saved in our electronic files. Results: A total of 209 patients were included in the study. The average age was 57.1 ± 17.1 years. The most common endoscopic findings were normal endoscopy in 76 patients (36.4%) and erosive esophagitis in 75 patients (35.9%). Barrett's esophagus and esophageal malignancy were encountered in 11 patients (5.3%) and 2 patients (0.95%), respectively. Esophageal biopsies were taken in 50.2% of patients, and one patient had histological evidence of EoE (0.5%). On univariate analysis, there was a trend for association between proton pump inhibitors (PPIs) use and a normal EGD, but it was not statistically significant (OR 0.28, 95% CI 0.07-1.11, p = 0.07). Conclusions: Endoscopic findings were prevalent in dysphagia patients even when no other alarm symptoms exist. Neoplastic lesions and EOE were rare in our study.

Clinical evaluation of pregnant women with SARS-COV2 pneumonia: a real-life study from Egypt.

BACKGROUND: Knowledge about the outcome of COVID-19 on pregnant women is so important. The published literature on the outcomes of pregnant women with COVID-19 is confusing. The aim of this study was to report our clinical experience about the effect of COVID-19 on pregnant women and to determine whether it was associated with increased mortality or an increase in the need for mechanical ventilation in this special category of patients. METHODS: This was a cohort study from some isolation hospitals of the Ministry of Health and Population, in eleven governorates, Egypt. The clinical data from the first 64 pregnant women with COVID-19 whose care was managed at some of the Egyptian hospitals from 14 March to 14 June 2020 as well as 114 non-pregnant women with COVID-19 was reviewed. RESULTS: The two groups did not show any significant difference regarding the main outcomes of the disease. Two cases in each group needed mechanical ventilation (p 0.617). Three cases (4.7%) died among the pregnant women and two (1.8%) died among the non-pregnant women (p 0.352). CONCLUSIONS: The main clinical outcomes of COVID-19 were not different between pregnant and non-pregnant women with COVID-19. Based on our findings, pregnancy did not exacerbate the course or mortality of COVID-19 pneumonia.

The Impact of Ramadan Fasting on Fatty Liver Disease Severity: A Retrospective Case Control Study from Israel.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed. OBJECTIVES: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores. METHODS: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of ß-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month. RESULTS: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005). CONCLUSIONS: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.

A comparative analysis of the efficacy and safety of therapeutic interventions in phlegmasia cerulea dolens.

OBJECTIVE: Present an institution's experience in management of phlegmasia cerulea dolens (PCD) with a review of the literature. METHODS: Beaumont Health's electronic record database was queried between July 2009 and November 2019 for inpatients with PCD. A comprehensive chart review was performed to verify the accuracy of the diagnosis and extract relevant parameters. Medians and proportions are reported. RESULTS: 22 patients met the criteria for PCD. 59% females. Median age 65 years (interquartile range [IQR] 22). Obesity was present in 45% of patients. 18 patients underwent either a single modality (55.5%) or a multimodality therapeutic approach (44.5%). Limb amputation was required in a third of patients who underwent catheter-directed thrombolysis or percutaneous thrombectomy alone. Death was highest after percutaneous thrombectomy alone (66%) followed by pharmacomechanical catheter-directed thrombolysis alone (50%). CONCLUSION: Percutaneous interventions have become the mainstay in management of PCD as demonstrated in this large retrospective analysis and supported by literature review.

Predictors of in-hospital mortality among patients with clostridium difficile infection: a multicenter study.

BACKGROUND: Clostridium difficile infection (CDI)-associated mortality is a major global health concern. Several clinical and laboratory parameters have been linked to poor prognosis in patients with CDI. In the current study, we aimed to assess the rate of in-hospital mortality among Israeli CDI patients and to look for clinical and laboratory parameters associated to death. METHODS: We performed a multicenter retrospective study enrolling all patients above 18-years old who were hospitalized for CDI or with diagnosis made during hospitalization in two regional, teaching hospitals in the north of Israel (Galilee Medical Center, Nahariya and the Nazareth Hospital, Nazareth, Israel), from January 1, 2015 until January 1, 2020. All files of eligible patients were reviewed for demographic (age, gender), medical history and laboratory tests. RESULTS: Overall, we included in the study 180 patients, among them 56 died in hospital due to CDI (group A) while 124 survived (group B). The average age in groups A and B was 77.02±13 vs. 71.5±19.1, respectively. On univariate analysis, several clinical and laboratory parameters were associated with in-hospital mortality, including: advanced age, renal failure, antibiotics treatment while on treatment for CDI, need for mechanical ventilation, level of hemoglobin, white blood cells (WBC) and neutrophils count, neutrophil/lymphocyte ratio, serum level of albumin, creatinine and C reactive protein. On multivariate logistic regression analysis, only 4 parameters showed statistically significant association with in-hospital mortality, including age (odds ratio [OR]: 6.97, 95%confidence interval [CI]: 4.94-8.72, P=0.003), renal failure (OR: 3.72, 95% CI: 1.22-11.24, P=0.02), WBC count (OR: 1.09, 95% CI: 1.02-1.16, P=0.008), and lower albumin level (OR: 47.62, 95% CI: 10.31-200, P<0.0001). CONCLUSIONS: In this retrospective, multicenter study, age, serum albumin level, leucocytes count, and renal failure were the main predictors of in-hospital mortality in patients with CDI. Thus, antibiotic use should be weighed carefully in elderly comorbid patients, at increased risk of mortality from CDI .Prospective multicenter randomized studies investigating the effect of albumin infusion on in-hospital death of CDI patients are needed, thus enabling us to direct monitoring and treatment accordingly.

Percutaneous thrombectomy of Impella-associated iliac artery thrombosis using the FlowTriever system.

Percutaneous thrombectomy using the FlowTriever system is a potentially safe and effective alternative to surgery in cases of Impella-associated peripheral arterial thrombosis.

Delayed Yet Successful Mechanical Thrombectomy for Phlegmasia Cerulea Dolens in a Limb with Severe Arterial Disease and May-Thurner Syndrome.

Phlegmasia cerulea dolens (PCD) is a rare but life-threatening complication of acute deep venous thrombosis that lacks consensus regarding the approach to management. We present a case of PCD developing shortly after a spinal surgery and manifesting as acute swelling and discoloration in a leg with existing severe atherosclerotic arterial disease. The patient's critical limb ischemia was completely and rapidly reversed by percutaneous mechanical thrombectomy using the ClotTriever device despite a delay in treatment. An underlying iliac vein compression "May-Thurner" syndrome was discovered using intravascular ultrasound and treated with angioplasty. This case identifies mechanical thrombectomy using the ClotTriever system as a possible effective and safe treatment for PCD.

Concomitant use of direct oral anticoagulants and aspirin versus direct oral anticoagulants alone in atrial fibrillation and flutter: a retrospective cohort.

BACKGROUND: The benefit of combining aspirin and direct oral anticoagulants on the reduction of cardiovascular events in atrial fibrillation or flutter is not well studied. We aimed to assess whether concurrent aspirin and direct oral anticoagulant therapy for atrial fibrillation or flutter will result in less coronary, cerebrovascular and systemic ischemic events compared to direct oral anticoagulant therapy alone. METHODS: Retrospective study of adult patients between 18 and 100 years old who have nonvalvular atrial fibrillation or flutter and were started on a direct oral anticoagulant (apixaban, rivaroxaban, or dabigatran), between January 1, 2010 and September 1, 2015 within the Beaumont Health System. Exclusions were history of venous thromboembolic disease and use of other antiplatelet therapies such as P2Y12 inhibitors. Patients were classified into two groups based on concurrent aspirin use and observed for a minimum of 2 years. Primary outcome was major adverse cardiac events, defined as acute coronary syndromes, ischemic strokes, and embolic events. Secondary outcomes were bleeding and death. RESULTS: Six thousand four patients were in the final analysis, 57% males and 80% Caucasians, median age 71, interquartile range (63-80). The group exposed to aspirin contained 2908 subjects, and the group unexposed to aspirin contained 3096 subjects. After using propensity scores to balance the baseline characteristics in both groups, the analysis revealed higher rate of major adverse cardiac events in the exposed group compared to the unexposed group, (HR 2.11, 95% CI (1.74-2.56)) with a number needed to harm of 11 (95% CI [9-11]). The rate of bleeding was also higher in the exposed group, (HR 1.30, 95% CI (1.11-1.52)). The rate of death was not statistically different between the groups, (HR 0.87, 95% CI (0.61-1.25)). CONCLUSIONS: In this observational analysis of patients with atrial fibrillation and flutter, the concomitant use of direct oral anticoagulants and aspirin was associated with an increased risk of both major adverse cardiac and bleeding events when compared to the use of direct oral anticoagulants alone. These findings underscore the potential harm of this combination therapy when used without a clear indication.

The association between non-alcoholic fatty liver disease and valvular heart disease.

BACKGROUND: Non-alcoholic fatty liver (NAFLD) disease has become the commonest cause of end-stage liver disease. Patients with NAFLD have an increased risk of associated extrahepatic conditions, including structural and functional cardiovascular disease. Still, it is unknown if there is an association between NAFLD and valvular heart disease (VHD). The aim of this paper was to determine the association between NAFLD and VHD. METHODS: We performed a single center retrospective study in EMMS Nazareth Hospital from April 2010 to April 2018. All patients who were diagnosed with NAFLD and who had an echocardiography performed within one year were included. Subjects age and sex-matched, who had echocardiography performed in the same period were included in the control group. RESULTS: The mean age of the NAFLD group was 41.5±11.7 vs. 42.8±10.8 years of the control group (P=0.2). The prevalence of aortic stenosis, aortic insufficiency, mitral stenosis and mitral insufficiency were significantly higher in NAFLD patients compared to the control group (1.2% vs. 0.22%, 1.32% vs. 0.32%, 0.66% vs. 0.27%, and 1.87% vs. 0.41%, respectively; P<0.001). In the multivariate logistic regression analysis, NAFLD was found to be independent risk factor for VHD (OR 2.39, 95% CI 2.17-2.78, P<0.001). CONCLUSIONS: VHD was significantly seen more frequently in NAFLD patients compared to controls. Prospective studies are needed to validate our findings and to elucidate the pathogenesis of VHD in patients with NAFLD.

Non-alcoholic fatty liver disease: a survey of involvement of primary care physicians.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are neglected in most patients' electrical medical report by their family physicians (FP). We have assessed whether family physicians have the proper knowledge of NAFLD and accurate training to diagnose and treat NAFLD/NASH in overweight and obese patients. METHODS: We conducted an anonymous survey questionnaire. Family Physicians who participated completed 4 years of residency and have passed the final examination. Our survey contained questions to measure the physician's attitudes, source of knowledge and recommendation regarding NAFLD/NASH treatment and attitudes toward patients with NAFLD/NASH. Categorical variables were extracted and analyzed using SPSS. RESULTS: A total of 310 of 422 FPs were included in the study with a compliance rate of 73%. Our data suggests that 167 of the 310 FPs (55%) refer their patients to a specialist for consultations if they exhibited fatty liver disease. Yet, 284 of 310 send their patients to consolations if exhibiting elevated liver enzyme. Our data significantly suggests that 241 of 310 (78%) reported that they have limited efficacy in treating NAFLD/NASH and consider themselves not properly prepared, by medical schools, to treat NASH/NAFLD patients; as well as patients with obesity and metabolic syndrome without fatty liver. CONCLUSIONS: FPs are more likely to neglect proper treatment for NAFLD/NASH due to lack of proper knowledge and are more likely neglect referring patients to specialist. Patients with significant obesity and obesity related conditions are more likely to have proactive treatment plans by their FPs.

Optimizing the Technique for Invasive Fractional Flow Reserve to Assess Lesion-Specific Ischemia.

BACKGROUND: Invasive fractional flow reserve (FFRINV) is the standard technique for assessing myocardial ischemia. Pressure distortions and measurement location may influence FFRINV interpretation. We report a technique for performing invasive fractional flow reserve (FFRINV) by minimizing pressure distortions and identifying the proper location to measure FFRINV. METHODS: FFRINV recordings were obtained prospectively during manual hyperemic pullback in 100 normal and diseased coronary arteries with single stenosis, using 4 measurements from the terminal vessel, distal-to-the-lesion, proximal vessel, and guiding catheter. FFRINV profiles were developed by plotting FFRINV values (y-axis) and site of measurement (x-axis), stratified by stenosis severity. FFRINV≤0.8 was considered positive for lesion-specific ischemia. RESULTS: Erroneous FFRINV values were observed in 10% of vessels because of aortic pressure distortion and in 21% because of distal pressure drift; these were corrected by disengagement of the guiding catheter and re-equalization of distal pressure/aortic pressure, respectively. There were significant declines in FFRINV from the proximal to the terminal vessel in normal and stenotic coronary arteries (P<0.001). The rate of positive FFRINV was 41% when measured from the terminal vessel and 20% when measured distal-to-the-lesion (P<0.001); 41.5% of positive terminal measurements were reclassified to negative when measured distal-to-the-lesion. Measuring FFRINV 20 to 30 mm distal-to-the-lesion (rather than from the terminal vessel) can reduce errors in measurement and optimize the assessment of lesion-specific ischemia. CONCLUSIONS: Meticulous technique (disengagement of the guiding catheter, FFRINV pullback) is required to avoid erroneous FFRINV, which occur in 31% of vessels. Even with optimal technique, FFRINV values are influenced by stenosis severity and the site of pressure measurement. FFRINV values from the terminal vessel may overestimate lesion-specific ischemia, leading to unnecessary revascularization.