Ponatinib-Related Vasospastic Angina.

Tyrosine kinase inhibitors (TKIs) are essential drugs for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Cardiovascular or arteriothrombotic adverse events have been reported in patients treated with TKIs. We report 3 cases of Ponatinib-related vasospastic angina, in which prophylactic administration of nitrates or calcium channel blockers was effective.

Impact of a national initiative to provide civilian cardiopulmonary resuscitation training courses on the rates of bystander intervention by citizens and survival after out-of-hospital cardiac arrest.

BACKGROUND: The impact of a national initiative to provide cardiopulmonary resuscitation (CPR) education to the public on the rates of citizen-initiated CPR and survival following out-of-hospital cardiac arrest (OHCA) remains uncertain. METHODS: We examined 358,025 cases of citizen-witnessed OHCA with presumed cardiac origin, recorded in the Japanese nationwide registry from 2005 to 2020. We assessed the relationship between the number of individuals certified in CPR courses, citizen interventions, and neurologically favorable survival at one month. RESULTS: The cumulative number of certified citizens has linearly increased from 9,930,327 in 2005 to 34,938,322 in 2020 (incidence rate ratio for annual number = 1.03, p < 0.001), encompassing 32.3% of the Japanese population aged 15 and above. Similarly, the prevalence of citizen-initiated CPR has consistently increased from 40.6% in 2005 to 56.8% in 2020 (P for trend < 0.001). Greater citizen CPR engagement was significantly associated with better outcome in initial shockable rhythm patients [chest compression only: odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02-1.51; P = 0.029; chest compression with rescue breathing: OR 1.33; 95% CI 1.08-1.62; P = 0.006; defibrillation with chest compression: OR 2.27; 95% CI 1.83-2.83; P < 0.001; defibrillation with chest compression and rescue breathing: OR 2.15; 95% CI 1.70-2.73; P < 0.001 vs. no citizen CPR]. CONCLUSIONS: The incidence of citizen-initiated CPR across Japan has consistently and proportionately increased with the rising number of individuals certified in CPR courses. Greater citizen CPR involvement has been linked to neurologically favorable survival, particularly in cases with an initial shockable rhythm.

2023 update and perspectives.

Total 276 manuscripts were published in Hypertension Research in 2022. Here our editorial members picked up the excellent papers, summarized the current topics from the published papers and discussed future perspectives in the sixteen fields. We hope you enjoy our special feature, 2023 update and perspectives in Hypertension Research.

Prognostic Impact of Reduced Left Ventricular Ejection Fraction After Endovascular Therapy for Lower Extremities.

BACKGROUND: The mechanism underlying a poor prognosis in patients with lower-extremity artery disease (LEAD) with heart failure is unknown. We examined the prognostic impact of the left ventricular ejection fraction (LVEF) in patients with LEAD who underwent endovascular therapy (EVT).Methods and Results: From August 2014 to August 2016, 2,180 patients with LEAD (mean age, 73.2 years; male, 71.9%) underwent EVT and were stratified into low-LVEF (LVEF <40%; n=234, 10.7%) and not-low LVEF groups. In the low- vs. not-low LVEF groups, there was a higher prevalence of heart failure (i.e., history of heart failure hospitalization or New York Heart Association functional class III or IV symptoms) (44.0% vs. 8.3%, respectively), diabetes mellitus, chronic kidney disease, below-the-knee lesion, critical limb ischemia, and incidence of major cardiovascular and cerebrovascular events (MACCEs) and major adverse limb events (MALEs) (P<0.001, all). Low LVEF independently predicted MACCEs (hazard ratio: 2.23, 95% confidence interval: 1.63-3.03; P<0.001) and MALEs (hazard ratio: 1.85, 95% confidence interval: 1.15-2.96; P=0.011), regardless of heart failure (P value for interaction: MACCEs: 0.27; MALEs: 0.52). CONCLUSIONS: Low LVEF, but not symptomatic heart failure, increased the incidence of MACCEs and MALEs. Intensive cardiac dysfunction management may improve LEAD prognosis after EVT.

Impact of COVID-19 Pandemic on Advanced Non-small Cell Lung Cancer Treatment at a Japanese Hospital.

Background/Aim: The COVID-19 pandemic has forced medical institutions to scale back their practice. Changes in patient behavior seemed to be having an impact. We conducted a survey with the aim of reviewing lung cancer treatment during the pandemic period and identifying problems. Patients and Methods: We examined the medical records of all patients pathologically diagnosed with non-small cell lung cancer (NSCLC) in our hospital from 2017 to 2022. NSCLC patients were divided into two groups: those diagnosed between 2017 and 2019 (first period) and those diagnosed between 2020 and 2022 (second period). Results: Within the study period, 267 NSCLC patients (first period: 147 patients, second period: 121 patients) were diagnosed in our hospital. The patients in the two study periods did not differ significantly in age (p=0.613), ECOG performance status (p=0.125), and clinical stage (p=0.354). Tumor size was significantly larger in the second period with a mean of 5.88 cm ± 3.02, compared to 4.24 cm ± 1.76 in the first period (p<0.001). In the standard treatment group, the median survival time was 457 days in the first period and 313 days in the second period (p=0.063). In the best supportive care group, median survival time was 122 days in the first period and 57 days in the second period (p=0.004). Conclusion: Patients themselves refrained from seeking consultation for lung cancer treatment during the pandemic period. It is inconclusive how to reduce the delay due to the suppression of consultations, but this is an important issue for the future.

The association of calcium channel blocker with risk of adverse limb events in patients with chronic limb-threatening ischemia after endovascular treatment.

Symptoms of lower-extremity artery disease (LEAD) emerge from impaired vascularization in distal circulation of the extremities. Calcium channel blockers (CCB) can improve distal circulation when used as adjunctive therapy with endovascular treatment (EVT), but few studies have evaluated that. We investigated the relationship between CCB therapy and post-EVT outcomes. Through a consecutive EVT registry, we evaluated those relationships in whole cohort and the following 2 subgroups; the patients suffered from intermittent claudication (IC) or chronic limb-threatening ischemia (CLTI), with adjusting baseline characteristics by propensity score matchings. The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE, a composite endpoint of all death, nonfatal myocardial infarction, and nonfatal stroke), and major adverse limb event (MALE, a composite of major amputation, acute limb ischemia, and surgical reintervention). The group that received CCB had less MALE in whole cohort (HR 0.31; 95% confidence interval (CI) 0.20-0.47), and less MACCE and MALE in CLTI cohort (HR 0.67; 0.50-0.89 and 0.32; 0.20-0.52 respectively) compared to the group that did not receive CCB. The relationships were common in the cohorts with baseline adjustment. MACCE and MALE in IC (HR 1.01; 0.57-1.80 and 0.60; 0.25-1.45, respectively) showed no significant differences both with and without baseline adjustment. CCB use was related to fewer MACCE and MALE events in adjusted patients who underwent EVT, and the trend was more evident, especially in the adjusted CLTI cohort. This study highlights the necessity of future studies regarding CCB. Clinical Trial Registration: URL: https://www.umin.ac.jp ; Unique identifiers: UMIN000015100.

Update in uric acid, hypertension, and cardiovascular diseases.

A direct relationship between serum uric acid levels and hypertension, cardiovascular, renal and metabolic diseases has been reported in many basic and epidemiological studies. Among these, high blood pression is one of the most common features associated with hyperuricemia. In this regard, several small-scale interventional studies have demonstrated a significant reduction in blood pressure in hypertensive or prehypertensive patients on uric acid-lowering drugs. These observation or intervention studies have led to affirm that there is a causal relationship between uric acid and hypertension. While the clinical association between uric acid and high blood pressure is notable, no clear conclusion has yet been reached as to whether lowering uric acid is beneficial to prevent cardiovascular and renal metabolic diseases. Recently, several prospective randomized controlled intervention trials using allopurinol and other uric acid-lowering drugs have been reported, and the results from these trials were almost negative, suggesting that the correlation between hyperuricemia and cardiovascular disease has no causality. However, it is important to note that in some of these recent studies there were high dropout rates and an important fraction of participants were not hyperuricemic. Therefore, we should carry caution in interpreting the results of these studies. This review article presents the results of recent clinical trials using uric acid-lowering drugs, focusing on hypertension and cardiovascular and renal metabolic diseases, and discusses the future of uric acid therapy.

Refusal of Subsequent Treatment in Patients With EGFR-mutant Non-small-cell Lung Cancer After Response to EGFR-TKIs.

BACKGROUND/AIM: During the course of effective and long-term treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), some elderly patients might decline further treatment after EGFR-TKI. We conducted a study to try and understand the reasons for this treatment decision. PATIENTS AND METHODS: We analyzed the medical records of all patients diagnosed with non-small-cell lung cancer with EGFR mutations between 2016 and 2021. RESULTS: There were 108 patients who received EGFR-TKIs. Of these, 67 patients responded to TKI. These responding patients were divided into two groups according to whether they received subsequent TKI treatment. At their request, 24 patients (group A) did not receive further anticancer treatment following TKI. The other 43 patients (group B) received anticancer therapy following TKI. Progression-free survival in group A patients was significantly longer (median=18 months, range=1-67 months) than in group B patients. The reasons for not wanting subsequent treatment after TKI were older age, reduced general condition, deterioration of physical comorbid disease and dementia. Dementia was the most common reason for patients over 75 years of age. CONCLUSION: Some elderly patients with well-controlled disease might express their refusal of all subsequent anticancer therapy after TKIs. Medical staff should respond seriously to these requests.

Comparison of the incidence of depression before and after endovascular treatment in patients with lower limb peripheral artery disease.

Depression is a chronic illness that affects mood, physical health, and overall vitality and quality of life. Depression has been associated with an increased risk of all-cause and cardiovascular mortality among patients with peripheral arterial disease (PAD). Therefore, this study aimed to compare the incidence of depression before and after endovascular treatment in patients with lower limb PAD. This is an important clinical issue considering the worldwide increase in PAD with the aging population and the known negative impact of depression on recovery. This was a retrospective sub-analysis of data from the Tokyo Peripheral Vascular Intervention Study using the TOMA-CODE registry. The presence and extent of depressive symptoms were evaluated using the patient health questionnaire (PHQ-9), with a depressive tendency score of ≥ 5. The PHQ-9 score was evaluated before endovascular treatment (EVT) and at 4 (± 1) weeks after EVT. The study population consisted of 87 patients who completed the PHQ-9 before EVT, with 76 completing the post-EVT PHQ-9. Of these 76, 19 had a pre-EVT score ≥ 5. Overall, there was no difference in the pre- and post-EVT scores (P = 0.091). There was no significant change in the 19 patients with a pre-EVT score ≥ 5 (mean 9.2 ± 4.4); however, there was a tendency to improve in the pre- to post-EVT score (mean, 6.9 ± 5.2; P = 0.059). Diabetes was a significant negative factor for pre- to post-EVT score improvement (P = 0.023). Overall, symptoms of depression showed the tendency to improve at 30 days post-EVT. However, diabetes was associated with lower improvement in symptoms.

Prognostic impact of atrial fibrillation on the outcomes of peripheral artery disease according to preoperative symptoms for endovascular revascularization.

Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences.

Xanthine oxidase inhibitors treatment or discontinuation effects on mortality: evidence of xanthine oxidase inhibitors withdrawal syndrome.

Objectives: This study investigates the impact of xanthine oxidase inhibitors (XOI) on mortality in patients with cardiovascular diseases. XOI withdrawal has been reported to increased mortality risk due to rapid adenosine triphosphate (ATP) deficiency. This study aims to determine whether XOI treatment reduces mortality and whether XOI withdrawal increases mortality. Methods: This is a real-world database study using the Japanese Registry of All Cardiac and Vascular Diseases (J-ROAD). We analyzed 1,648,891 hospitalized patients aged 20-90 with acute coronary syndrome or heart failure. In the first study, mortality rates were compared between patients without urate-lowering agents (n = 1,292,486) and those with XOI agents (n = 315,388, excluding 41,017 on other urate-lowering agents). In the second study, mortality rates were compared between the XOI continuous medication group (n = 226,261) and the XOI withdrawal group (n = 89,127). Results: After multiple adjustments, XOI treatment group showed significantly lower mortality compared with that without any urate-lowering agent (odds ratio (OR), 0.576, 95% confidence interval (CI), 0.567-0.587, p < .001). In the sub-analysis, the group with allopurinol (OR, 0.578; 95% CI, 0.557-0.600), febuxostat (OR, 0.610; 95% CI, 0.599-0.622), and topiroxostat (HR, 0.545; 95% CI, 0.473-0.628) showed lower OR of mortality compared with that without any urate-lowering agent. XOI withdrawal group led to significantly higher death rates compared to XOI continuous group (19.8% vs. 0.03%; p < .001). Conclusion: XOI treatment for patients with cardiovascular diseases is associated with reduced mortality. Conversely, XOI withdrawal is linked to elevated mortality risk. This emphasizes the importance of both prescribing and discontinuing XOI carefully to optimize patient outcomes.

Successful endovascular repair of complicated pseudoaneurysm using Perclose ProGlide: A novel concept.

Iatrogenic pseudoaneurysm is common vascular complications of angiographic procedures. Patients with uncomplicated pseudoaneurysms can be managed with ultrasound-guided techniques. However, for complicated pseudoaneurysms, surgical repair of the artery is mandatory. We report a case of successful repair of complicated pseudoaneurysm using an access-site closure device, Perclose ProGlide™ without a surgical approach.

Impediments to Heart Transplantation in Adults With MELASMT-TL1:m.3243A>G Cardiomyopathy.

BACKGROUND: The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. OBJECTIVES: We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. METHODS: The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. RESULTS: The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. CONCLUSIONS: High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.

Discontinuation of Immune Checkpoint Inhibitor and Survival in Patients With Non-small-cell Lung Cancer Without a Driver Gene Mutation.

BACKGROUND/AIM: Patients with non-small-cell lung cancer treated with immune checkpoint inhibitors (ICI) might be forced to discontinue treatment for various reasons. We conducted a retrospective study to evaluate the impact of discontinuation of ICI treatment on patient prognosis. PATIENTS AND METHODS: We performed a retrospective study that reviewed the medical charts of 86 patients treated with ICI monotherapy and 34 patients treated with a combination of ICI and chemotherapy during the period from February 2016 to February 2022 at our two hospitals. 'Discontinuation' was defined as a cessation of ICI treatment for more than two cycles for any reason. RESULTS: The two most common reasons for discontinuation were immune-related adverse events and at the request of the patient. Nineteen patients who had discontinued ICI, resumed ICI or another therapy. Discontinuation of ICI treatment was a favorable factor in overall survival in 84 patients with ICI monotherapy as well as in 34 patients treated with chemotherapy combined with ICI. CONCLUSION: This analysis found discontinuation of ICI treatment did not adversely affect prognosis. This suggests that when treating patients with non-small-cell lung cancer with ICI, chest physicians should respond flexibly, and, with careful monitoring, consider discontinuation of ICI.

Update on Hypertension Research in 2021.

In 2021, 217 excellent manuscripts were published in Hypertension Research. Editorial teams greatly appreciate the authors' contribution to hypertension research progress. Here, our editorial members have summarized twelve topics from published work and discussed current topics in depth. We hope you enjoy our special feature, "Update on Hypertension Research in 2021".

Body Weight Change in Non-small Cell Lung Cancer Patients Treated With EGFR-TKI.

BACKGROUND/AIM: Body weight (BW) changes in epidermal growth factor inhibitor-tyrosine kinase (EGFR-TKI) treated non-small cell lung cancer patients has yet to be fully investigated. For the purpose of clarifying changes in body weight in patients who received EGFR-TKI treatment in clinical practice, we performed a retrospective study. In this study, comparison between pretreatment BW and those at 12, 24 weeks, and 12 months in these patients was performed. PATIENTS AND METHODS: We included all the patients diagnosed with EGFR mutated NSCLC in two tertiary hospitals between April 2009 and March 2021. BW records in the medical chart of each patient who was treated with EGFR-TKI for more than 12 weeks were surveyed. In each patient, BW at 12, 24 weeks, and 12 months from the initiation of EGFR-TKI treatment were compared with pretreatment BW. RESULTS: Sixty-three patients obtained TKI treatment for more than 12 weeks and had comparable body weight records. Compared with the pretreatment BW, decreased BW was observed at 12, 24 weeks, and 12 months from the initiation of TKI treatment. CONCLUSION: Even in patients treated with EGFR-TKI, which is evaluated as less toxic and a more effective therapy, there might be patients who lose weight during the treatment period. Chest physicians will be required to provide medical care even for EGFR mutated patients, taking into consideration changes in BW.

Left atrial dissection associated with disruption of mitral annular calcification: a case report.

Background: Left atrial dissection is an uncommon entity associated with cardiac surgery, catheter interventional procedures, or cardiac trauma. Spontaneous cases have also been reported. The entry of left atrial dissection often occurs in the posterior annulus of the mitral valve, which is also a favourable site for mitral annular calcification (MAC). We herein report a rare case of spontaneous left atrial dissection caused by a disruption of MAC. Case summary: An 84-year-old woman was admitted to our hospital for chest discomfort. Transthoracic echocardiography showed severe calcification of the posterior mitral annulus and a heterogeneous mass in the posterior wall of the left atrium adjacent to MAC. Transoesophageal echocardiography showed blood flow through MAC from the left ventricle into the mass. Cardiac computed tomography showed the disruption of MAC, which was the entry for left atrial dissection and haematoma. The conservative approach was continued, as the haemodynamic state was stable and because of her frailty and many complications. No further events occurred during 6 months follow-up, although the false cavity did not regress. Discussion: The diagnosis of an intracardiac mass can be challenging. In our case, a detailed anatomical evaluation with multiple imaging modalities allowed us to understand the disease and manage it appropriately.

Common exacerbation-prone phenotypes across asthma and chronic obstructive pulmonary disease (COPD).

BACKGROUND AND OBJECTIVES: Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes. METHODS: The study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses using non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130). RESULTS: Two-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34-11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45-5.15), p = 1.9 × 10-3). DISCUSSION: Our results indicated that the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases.

Impact of body mass index on the outcome of Japanese patients with cardiovascular diseases and/or risk factors hospitalized with COVID-19 infection.

BACKGROUND: Obesity is reported to be a predictor of adverse clinical events in coronavirus disease 2019 (COVID-19) in Western countries. However, there are limited data reported regarding the prognostic impact of obesity in Asian patients. We investigated the relationship between body mass index (BMI) and in-hospital outcomes in 580 Japanese patients with cardiovascular disease and/or risk factors and who were admitted for COVID-19 infection using data from 49 hospitals in Japan. METHODS: We analyzed data from the Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Disease and/or Risk Factors (CLAVIS-COVID) registry. BMI was classified into four groups accordance with the definition of the Japan Society for the Study of Obesity, as follows: underweight, <18.5 kg/m2; normal range, 18.5 to <25 kg/m2; pre-obese, 25 to 30 kg/m2; and obese, ≥30 kg/m2. RESULTS: In-hospital death occurred in 15.0% (n=87) of the patients and intubation was performed for 139 (24.0%) patients. In a multivariate analysis, we found a significant association between higher BMI and in-hospital mortality [underweight: hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.23-0.97; p=0.041; pre-obese: HR 1.46, 95%CI 0.84-2.55; p=0.18; and obese: HR 3.28, 95%CI 1.34-8.02; p=0.009 vs. normal range]. In contrast, the association between BMI and the intubation rate was not statistically significant. CONCLUSIONS: Obesity was associated with a stepwise increase in the risk of in-hospital mortality in Japanese patients with COVID-19 infection. The threshold BMI for the increased risk of a worse outcome was 30, which was much lower in comparison to Western countries.

The "bud" of an aortic aneurysm.

An overlooked "bud" of an aortic aneurysm on a chest radiography resulted in a saccular aortic aneurysm 9 years later. This eye-catching image showed us the importance of not only documenting abnormalities in regular radiography but also further imaging evaluation for definitive diagnosis and continuous image follow-up.