Flash'O real-world evidence programme - Attitude and practices toward the use of omega-3 FA by physicians from Middle East Countries.

The Flash'O project was designed to provide insights into the current use of prescription omega-3 and their perceived benefits by physicians in real-world clinical practice, in Russia, Saudi Arabia, Thailand, and Gulf countries, and to determine the adherence of physicians to dyslipidemia management guidelines. The present study focuses on Flash'O's process and results in Middle East countries. A total of 338 physicians and specialists completed the online questionnaire. Most responding physicians were male (91.7%), general practitioners (42.6%) with more than 5 years of seniority (80.4%) and saw more than 50 patients a week (71.5%). Most surveyed physicians (64.2%) reported using guidelines in their daily practice for the management of their patients with dyslipidemia. They mostly followed national guidelines (68.6%). American or European ones were less commonly used. Responding physicians thought that omega-3 supplementation could be more beneficial in all types of dyslipidemia, except high non- hight density lipoproteins, and for patients suffering from obesity, type 2 diabetes mellitus, acute coronary syndrome with ST-segment elevation myocardial infarction and high cardiovascular diseases risk (score ≥ 5% and < 10%), but less beneficial in chronic kidney disease. Respondents recommended omega-3 to their patients mainly after statin treatment in patients with dyslipidemia and for the treatment of dyslipidemia. This survey confirmed that omega-3 fatty acids are at the heart of the cardiovascular medical strategy.

The Prevention and Cardiac Rehabilitation Group of the Saudi Heart Association Recommendations Regarding Establishing a Cardiac Rehabilitation Service.

Cardiac rehabilitation (CR) is a cornerstone in the secondary prevention of cardiovascular disease (CVD). Comprehensive cardiac rehabilitation has obtained the highest class of recommendation and the level of evidence for the treatment of patients with ST-segment elevation myocardial infarction, after myocardial revascularization, with chronic coronary syndromes, and in patients with heart failure (HF). Comprehensive cardiac rehabilitation should be implemented as soon as possible, be multi-phasic, and adjusted to the individual needs of the patient. CR is still suboptimally used, and many cardiac centers do not have such services (2). The provision of CR services should be based on standards and key performance indicators, and guidelines containing a minimum standard of cardiac rehabilitation utilization should be published to improve the quality of the CR program. This document presents an expert opinion that summarizes the current medical knowledge concerning the goals, target population, organization, clinical indications, and implementation methods of the CR program in the Kingdom of Saudi Arabia.

Echocardiographic Imaging in Transcatheter Structural Intervention: An AAE Review Paper.

Transcatheter structural heart intervention (TSHI) has gained popularity over the past decade as a means of cardiac intervention in patients with prohibitive surgical risks. Following the exponential rise in cases and devices developed over the period, there has been increased focus on developing the role of "structural imagers" amongst cardiologists. This review, as part of a growing initiative to develop the field of interventional echocardiography, aims to highlight the role of echocardiography in myriad TSHIs available within Asia. We first discuss the various echocardiography-based imaging modalities, including 3-dimensional echocardiography, fusion imaging, and intracardiac echocardiography. We then highlight a selected list of structural interventions available in the region-a combination of established interventions alongside novel approaches-describing key anatomic and pathologic characteristics related to the relevant structural heart diseases, before delving into various aspects of echocardiography imaging for each TSHI.

Association Between COVID-19 Infection and Cardiac Biomarkers in Hospitalized Patients at a Tertiary Care Center.

Background The effects of coronavirus disease 2019 (COVID-19) on the cardiovascular system are well established. However, knowledge gaps in the clinical implications of cardiac involvement in COVID-19 patients are yet to be addressed. This study aimed to investigate acute cardiac injury (ACI) risk factors and outcomes associated with COVID-19 infection with cardiac involvement. Methodology In this retrospective study, we included hospitalized patients between March 2020 and May 2022 with confirmed COVID-19 infection and evidence of cardiac involvement. Results In total, 501 patients were included, of whom 396 (79%) had evidence of ACI. The median troponin level was 25.8 (interquartile range (IQR) = 10.8-71). Patients with evidence of ACI were significantly more likely to have diabetes mellitus (75% vs. 60%), cardiovascular disease (48% vs. 37%), chronic lung disease (22.2% vs. 12.4%), and chronic kidney disease (32.3% vs. 16.2%). Additionally, patients with ACI were significantly more likely to have cardiomegaly (60.6% vs. 44.8%) and bilateral lobe infiltrates (77.8% vs. 60%) on X-ray. Patients with ACI were significantly more likely to suffer from complications such as cardiogenic shock (5.3% vs. 0%), pneumonia (80.1% vs. 65.7%), sepsis (24.2% vs. 9.5%), and acute respiratory distress syndrome (33.1% vs. 8.6%). Patients with ACI were also significantly more likely to be admitted to the intensive care unit (ICU) (57% vs. 26.7%) and significantly more likely to die (38.1% vs. 11.4%). The results of the multivariate regression analysis indicated that mortality was significantly higher in patients with elevated troponin levels (adjusted odds ratio = 4.73; 95% confidence interval = 2.49-8.98). Conclusions In COVID-19-infected patients, old age, diabetes mellitus, cardiovascular disease, chronic lung disease, and chronic kidney disease were associated with an increased risk of ACI. The presence of ACI in the context of COVID-19 infection was noted to increase the risk for severe complications, such as cardiogenic shock, ICU admission, sepsis, and death.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

AIM: To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. BACKGROUND: The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. OBJECTIVE: Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. METHODS: The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipidlowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. RESULTS: Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. CONCLUSION: The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Correlation Between Different Parameters of Acute Myocardial Infarction and Obesity.

OBJECTIVE: To study if obesity had a detrimental effect on troponin after acute coronary syndrome. We investigated the effects of the body mass index (BMI) in post-myocardial infarction (MI) patients, and see the difference in troponin levels and other parameters between normal and overweight patients. METHODOLOGY: A retrospective cohort study was conducted. Data were extracted from the electronic medical files of patients hospitalized due to acute ST-elevation MI to examine the association between BMI and MI. Sixty-one patients were categorized into normal BMI category, overweight, and obese/morbid obesity groups using the baseline measurements, to assess the independent factors associated with a patient with a high BMI who had a MI. RESULTS: In total, 61 post-myocardial infarction patients with a mean age of 56.9 ± 11.2 years were included in the study. The average BMI was 28.5 ± 6.5 kg/m2. Just more than a third (37.4%, n=23) were in the normal BMI category, 19 (31.2%) overweight, and 19 (31.2%) obese/morbid obesity. The mean left ventricle mass was 93.74 ± 32.69 gram and the mean left ventricular ejection fraction was 44.02% ± 10.02. A significant difference in the mean level of troponin and mean heart rate between the body mass index groups (normal vs. overweight groups) was noted. A fair correlation was noted between BMI and left ventricle mass. No statistically significant relation could be linked to high BMI with total cholesterol, low-density lipoprotein (LDL), or aspartate transferase/alanine transaminase (AST/ALT) levels. CONCLUSIONS: In this pilot study, the group with a high BMI had a statistically significant lower troponin level and higher mean heart rate. Such data need to be considered when assessing a patient's risk. In addition, obese persons with a MI had a higher left ventricle mass.

Severe Rheumatic Mitral Stenosis, Worse Left Atrial Mechanics is Closely Associated with Echo Criteria for Intervention.

Background: Rheumatic mitral valve (MV) stenosis is associated with progressive left atrial (LA) fibrosis and functional impairment, Pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction. The aims of the study were to determine in those patients with severe MV stenosis if LA mechanical function as assessed by speckle tracking echocardiography could identify those with increased PASP, atrial fibrillation (AFib), and RV dysfunction. Subjects and Methods: Patients with severe MV stenosis were identified from the institutional echo database. Echocardiograms were read off line and measurements included atrial and ventricular strain. Patients were divided into tertiles of LA reservoir strain (LASr) values and data compared between the groups. Results: Ninety-seven patients, 67 females, mean age 47.4 ± 11.9 years, had MV mean gradient of 8.3 ± 5.1 mmHg, MV area by pressure half time of 1.3 ± 0.3 cm2 and LASr of 11.18% ± 6.4%. Those patients in the lowest LASr tertile had more AFib (72%, P = 0.0001), PASP >50 mm Hg (39%, P = 0.005), and worst RV impairment. In multivariable logistic regression analysis, LASr, age, and mean MV gradient were the independent predictors of AFib and PASP >50 mm Hg. Cutoffs, determined by receiver operating characteristic curve analysis had high specificity for the composite outcome of Afib and PASP >50 mmHg (85% for LASr <7.7%). Conclusion: In severe MV stenosis LASr, age and mean MV gradient, are independent predictors of Afib and PASP >50 mmHg. LASr <7.7% has high sensitivity and specificity in identifying those who meet ESC guideline 2017 criteria for valve intervention, suggesting its potentially helpful addendum to the surveillance of patients with MV stenosis.

Right-sided infective endocarditis and pulmonary embolism: a multicenter study.

The incidence of right-sided infective endocarditis (RSIE) is steadily increasing and it has been reported to be associated with high risk of embolic events (EE). Aim of our study was to identify the clinical characteristics of patients with RSIE complicated by PE. Indeed, the identification of patients at high risk of significant PE who will benefit from a more aggressive therapeutic strategy may improve the prognosis. From January 2015 to September 2020, 176 patients (Pts) in 6 centers were found to have definite RSIE complicated by PE. Advanced imaging for PE including computed tomography pulmonary angiography (CTPA) was performed in 28 pts (16%) who represent our study group (24 male, mean age 50.6 ±18.29 years). They all underwent transesophageal echocardiography (TEE), in 12 cases (43%) also three-dimensional (3D) TEE, and 27 patients (99%) had both TEE and transthoracic echocardiography (TTE). A total of 53 vegetations (V) were detected. In 18 pts (64%) two or more vegetations were found. Native tricuspid valve was the most frequently involved valve (38 V, 71.7%), followed by catheter (5 V, 9.4%), tricuspid valve prosthesis (4 V, 7.5%), chordae and papillary muscle (2 V, 3.8%) and one vegetation (9%) in each of the following: pulmonic valve, inferior vena cava, eustachian valve, and right atrium. The most common location for vegetations was the anterior leaflet of the tricuspid valve (19 V, 35.8 %) followed by the posterior leaflet (11 V, 20.8%). The most common vegetations morphology was raceme-like shaped (35.8%). Staphylococcus aureus (S. aureus) was the most common causative pathogen (14 pts, 50%). The incidence of PE was very high in patients with vegetation length above 1.5 cm (median 17.6±6.5 mm by TEE). Our results suggest that a routine CTPA should be advised in the presence of vegetations larger than 1.5 cm and with S. aureus infection. This behavior would identify patients at high risk of PE who will benefit from a more aggressive therapeutic strategy, leading to an improvement in the prognosis. Further prospective studies are required to better confirm our hypothesis.

Identification of Novel and Known LDLR Variants Triggering Severe Familial Hypercholesterolemia in Saudi Families.

BACKGROUND: Familial hypercholesterolemia (FH) is a common illness mainly caused by variants occurring in the low-density lipoprotein receptor (LDLR) gene. FH is a leading cause of coronary artery disease. OBJECTIVE: This study aims to determine genetic defect(s) in homozygous and heterozygous FH index patients and their first-degree blood relatives and understand the genotype-phenotype correlation. METHODS: This study employed the genetic screening of FH-related genes by next-generation sequencing and cascade screening by capillary sequencing. RESULTS: We identified the presence of a novel frameshift variant [c.335_336insCGAG, p.(F114Rfs*17)] and three known missense variants [c.622G>A, p.(E208K)], [c.1474G>A, p.(D492N)], [c.1429G>A, p.(D477N)] in the LDLR gene of four unrelated Saudi families with FH. In proband 1, a nonsense variant c.1421C>G, p.(S474*) was also detected at exon 9 of the lipoprotein lipase gene. The segregation arrangement of the identified variants corresponded with the clinical characteristics. In this study, all the detected variants were confined in the ligand-binding domain and epidermal growth factor (EGF)-precursor homology domain of the LDLR protein, which portrayed severe clinical phenotypes of FH. Moreover, these LDLR variants were in a highly conserved residue of the proteins. CONCLUSION: In addition to the finding of the novel variant in the LDLR gene that extends the spectrum of variants causing FH, the results of this study also support the need for diagnostic screening and cascade genetic testing of this high-risk condition and to understand the genotype-phenotype correlation, which could lead to better prevention of coronary artery disease.

Loss of engagement in controlling chronic anticoagulation therapy during Covid-19 stringency measures. A single center experience of disproportioned increase of stuck mechanical valves.

Stuck valve is a very rare and severe complication that occurs in mechanical valve replacement patients with ineffective anticoagulation. However, with COVID-19 restriction measures, it became challenging to regularly assess INR to make sure it falls within the target therapeutic range to prevent this complication. We present a series of 10 patients who either underwent transthoracic echocardiography for a suspected stuck valve or were seen at the outpatient valve clinic with the residual consequences of a stuck valve during the COVID-19 restriction measures in our institute. Stuck prosthetic valves incident has increased significantly during this period, particularly those in the mitral position for which urgent replacement and prolonged hospitalization were necessary. Particularly with the COVID-19 restrictions in place, these cases highlight the need for physicians to be aware of the dramatic increase in the incidence of stuck prosthetic valves in patients on chronic warfarin therapy.

Complications of White-coat Hypertension Compared to a Normotensive and Hypertensive Population.

BACKGROUND: Accumulating evidence demonstrates that white-coat hypertension (WCH) are associated with several risks and complications. In this study, we aimed to investigate the adverse effects of WCH compared with hypertensive and normotensive patients. METHODS: A retrospective cohort study was conducted over five years. Blood pressure (BP) data was collected from both clinic visits and 24-h ambulatory blood pressure monitoring (ABPM) reports. Epidemiological data and complications, cardiac and noncardiac, were also recorded. RESULTS: In total, 286 participants who were followed up for at least three years were included. The sample was divided into 99 normotensive patients (as a control group), 94 patients with clinically diagnosed hypertension (HTN), and 93 patients with WCH. Ischemic heart disease (IHD) was the most noted complication in the WCH group with a relative risk of 9.58 (1.23-74.16) (P = 0.008). Acute coronary syndrome (ACS) was significantly correlated with a relative risk of 2.06 (0.52-13.38). No significant correlation was noted with noncardiac complications. Both HTN and WCH groups showed a significant association with blood pressure variability (BPV). WCH was associated with an increased BPV in ambulatory daytime systolic measurements (P = 0.031) and a unique increase in diastolic measurement variability in office BP measurements (P = 0.020). CONCLUSION: WCH should be managed as HTN. WCH is associated with cardiac complications, particularly IHD, specifically in patients 55 years and older. WCH was significantly associated with a higher BPV in both ABPM and office-based measurements.

A Community-Based, Cross-Sectional Study Assessing the Level of Awareness and Insight Related to Cardiovascular Diseases.

Objective The disease outcome had been shown to improve with improving patient knowledge. The study had two objectives, firstly to assess the level of knowledge about cardiovascular diseases (CVDs) in the general population, and secondly, to provide written educational material regarding the risk factors, major symptoms, and the prevention of CVDs. Method The target population was the residents living in the Western region of Saudi Arabia, aged 18 years and above. All were invited to participate voluntarily. A pre-structured questionnaire was designed to collect data related to age, gender, marital status, education level, occupation, lifestyle habits, and a history of heart diseases, as well as cardiac symptoms, and risk factors. The educational material was provided after the questionnaire. Results The majority of the participants were female (74.8%). The risk factors most frequently identified were lack of exercise, stress, and obesity. Chest pain was recognized as a major symptom (87.6%). Other symptoms included dyspnea, syncope, and excessive sweating. The level of knowledge regarding the risk factors for cardiovascular disease was poor. Only 18.5% were knowledgeable about the risk factors. The majority (60%) could identify the preventable factors, including smoking cessation (92.2%), a high level of cholesterol (88.6%), and hypertension (78.7%). The majority (83.7%) read the educational material and 99% reported that the lecture increased their knowledge about cardiovascular disease. Conclusion Although cardiovascular risk factors are common, there is a big gap in the knowledge in our population. Further, alarming symptoms that bring the patients to medical care are also deficient. A call for action at different levels is urgent. Simple educational material in a basic language and virtual education are useful and cheap tools that must be practiced wherever possible. Education is welcomed by the participants.

A Field-Based Study of the Magnitude of Risk Factors and Health Habits in Young Volunteers in the Community.

Objective A field study is more informative in terms of epidemiological data than a hospital-based study. Undiagnosed risk factors may be discovered in an asymptomatic group. This study aimed to estimate if the community was well informed about the risk factors for coronary artery disease and if that affected the prevalence and the anthropometric among those who participated in the study. Materials and methods A cross-sectional study was conducted, using a consecutive sampling technique. Individuals were interviewed in terms of the risk factors and clinical signs and symptoms. The anthropometric measurements were done on-site to identify asymptomatic risk factors. The survey was utilized to increase the awareness among the participants. Results In total, 193 individuals participated in this study. The mean age of the sample was 36.3 ± 12.4 years, with 53% male. Smoking was the most frequent risk factor (31.6%), followed by dyslipidemia (22.5%), hypertension (16.6%), and diabetes mellitus (14.5%). Almost half of the sample participated in sports for one to two hours per week (40%). Almost all consumed fast food at least once a week, and 16.6% consumed fast food more than four times a week. The average systolic blood pressure was 129.41 ± 22.5 mmHg and the average body mass index (BMI) 27.6 ± 7.2 kg/m2. Conclusion Dyslipidemia was the most prevalent risk factor. Hypertension and diabetes mellitus are on top of the risk factor pyramid in commonality. An early diagnosis is important to decrease the incidence of cardiovascular disease. The consumption of fast food and obesity are relatively high and require educational interventions and more available healthy food. Screening through social media and primary health care centers may avert a negative outcome.

Familial Hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain). METHODS: The multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up. RESULTS: Among 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons). CONCLUSIONS: This snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a "call-to-action" for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.

Gender differences in patients presenting with non-ST segment elevation myocardial infarction in the STAR registry.

BACKGROUND: In most acute coronary artery (ACS) related literature, the female gender constitutes a smaller proportion. This study is based on gender-specific data in the Saudi Acute Myocardial Infarction Registry Program (STARS-1 Program). A prospective multicenter study, conducted with patients diagnosed with ACS in 50 participating hospitals. RESULTS: In total, 762 (34.12%) patients were diagnosed with non-ST segment elevation myocardial infarction. Of this group, only 164 (21.52%) were women. The mean age (64.52 ± 12.56 years) was older and the mean body mass index (BMI) was higher (30.58 ± 6.23). A significantly proportion was diabetic or hypertensive; however, a smaller proportion was smoking. Hyperlipidemia was present in 48%. The history of angina/MI/stroke and revascularization was similar, except for renal impairment. The presentation was atypical as only 70% presented with chest pain, and the rest with shortness of breath or epigastric pain. At presentation, the female group were more tachycardiac, had higher blood pressure, and a higher incidence of being in class 11-111 Killip heart failure. Only 32% had a normal systolic function, and the majority had either mild or moderate systolic dysfunction. In particular, the rate of percutaneous coronary intervention was similar. The in-hospital mortality was similar (5%), with more women diagnosed with atrial fibrillation and heart failure at follow-up. CONCLUSIONS: Women had a higher prevalence of risk factors affecting the presentation and morbidity but not mortality. Improving these risk factors and the lifestyle is a priority to improve the outcome and decrease morbidity.

Embolisation of the Coronary Arterial Tree with Thick Contrast Material during Coronary Angiography.

A 58-year male was referred to our centre with an acute inferior ST elevation myocardial infarction (STEMI). During the primary percutaneous coronary intervention, he suddenly collapsed with severe hypotension and severe bradycardia. The symptoms were attributed to an accidental embolisation of his left coronary system with the thick contrast material. When the remaining contrast in the bottle was investigated, it contained abnormally thick contrast material. This is a rare case of contrast embolisation, which is completely preventable but fatal, if undetected. Key Words: Coronary angiography, Contrast material, Contrast embolisation.

The Myth of Myocardial Infarction With Normal Coronary Angiography.

Myocardial infarction with no obstructive atherosclerosis is an increasingly recognized presentation of acute coronary syndrome (ACS). The disease has all the clinical features of an ACS, but the only exception is that the coronary angiogram indicates non-obstructive coronary artery disease. Although different pathophysiological mechanisms have been postulated, no definitive mechanism has been identified. Consequently, the treatment plan varies and depends on the more probable mechanism. Here, we review the current body of knowledge about this disease and discuss updated management strategies.

Diagnóstico ecocardiográfico de una hernia de hiato. Reporte de un caso / Echocardiographic diagnosis of a Hiatus Hernia: A case report

The diagnosis of a hiatus hernia (HH) is typically confirmed with an upper gastrointestinal barium X-ray, gastroscopy or upper-intestinal endoscopy. In several cases, HH has been diagnosed with an echocardiogram. We here describe a case of an HH visible on an echocardiogram in a male patient with chest pain.

Transverse sinus mass misinterpreted as the source of cardiac emboli.

Due to the proximity of the transvers sinus (TS) to the left atrial appendage (LAA) and pulmonary veins (PV), a mass in the TS can be misinterpreted as a LAA or PV thrombus, and considered as a source of emboli in a patient with stroke or transient ischemic attack. The incorrect identification of a mass as a LAA thrombus would initiate unnecessary anticoagulation therapy or potentially, an evaluation for the excision of the mass if there is a concern about dislodgement. We are presenting a case illustrating this confusion and review the literature for similar cases.