Suction-based catheter retrieval of right ventricular clot-in-transit.

Right ventricular clot-in-transit (CIT) is a rare finding in venous thromboembolic disease and carries a high mortality rate. Its optimal treatments have yet to be established in the literature. Here we describe the usage of a suction-based catheter, the INARI FlowTriever® system (INARI Medical Inc.) to successfully retrieve a CIT from the right ventricle of a patient with coronavirus disease 2019 acute respiratory distress syndrome on veno-veno extracorporeal membrane oxygenation.

Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports.

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain. Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA). Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information. Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.

Incidence and risk factors for venous thromboembolism events after different routes of pelvic organ prolapse repairs.

BACKGROUND: Venous thromboembolism events, including deep venous thrombosis and pulmonary embolism are the most common cause of preventable deaths in hospitalized patients in the United States. Although the risk of venous thromboembolism events in benign gynecologic surgery is generally low, the potential for venous thromboembolism events in urogynecologic population is significant because most patients undergoing the pelvic organ prolapse surgery have increased surgical risk factors. OBJECTIVE: This study aimed to investigate the incidence and risk factors for venous thromboembolism events within 30 days after different routes of the pelvic organ prolapse surgery in a large cohort population using the American College of Surgeons-National Surgical Quality Improvement Program. STUDY DESIGN: This retrospective cohort study used Current Procedural Terminology codes to identify pelvic organ prolapse repairs with and without concurrent hysterectomy performed during 2011-2017 in the American College of Surgeons-National Surgical Quality Improvement Program database. Demographics, preoperative length of hospital stay, operative time, preoperative comorbidities, smoking status, American Society of Anesthesiologists classification system scores, along with other variables were collected. Postoperative 30-day complications, including readmission, reoperation, and mortality, were collected. The incidence rates of venous thromboembolism, as defined by American College of Surgeons-National Surgical Quality Improvement Program, were compared among different surgical routes. Descriptive statistics were used, and logistic regression was performed to identify associations. RESULTS: Among 91,480 pelvic organ prolapse surgeries identified, 63,108 were analyzed: 43,279 (68.6%) were performed vaginally, 16,518 (26.2%) laparoscopically, and 3311 (5.2%) abdominally. A total of 34,698 (55.0%) underwent a concurrent hysterectomy. Of 63,108 subjects, 133 developed venous thromboembolism within 30 days after surgery (0.21%; 95% confidence interval, 0.18-0.25; P<.0001). More than half (60%) of venous thromboembolism events occurred within 10 days after surgery. For all surgical routes, older age (P<.041), higher body mass index (P=.002), race or ethnicity (P=.04), longer operating time (P<.0001), inpatient status (P<.0001), American Society of Anesthesiologists 3 or 4 (P<.0001), having preoperative renal failure (P=.001), and chronic steroid use (P=.02) were significantly associated with venous thromboembolism. In addition, in the vaginal pelvic organ prolapse repair group, concurrent hysterectomy (P=.03) and preoperative dyspnea (P=.01) were associated with development of venous thromboembolism. In the abdominal pelvic organ prolapse repair, concurrent hysterectomy (P=.005) and hypertension requiring medication (P=.04) were also independently associated with venous thromboembolism development (Table 1). The incidence of venous thromboembolism was highest in abdominal repairs (0.72%), followed by laparoscopic repairs (0.25%) and vaginal repairs (0.16%). After adjusting for confounders, abdominal compared with vaginal approach (adjusted odds ratio, 3.27; 95% confidence interval, 1.93-5.41; P<.0001), longer operative time (adjusted odds ratio, 1.005; 95% confidence interval, 1.003-1.006; P<.0001), older age (adjusted odds ratio, 1.020; 95% confidence interval, 1.00-1.037; P=.015), greater body mass index (adjusted odds ratio, 1.04; 95% confidence interval, 1.01-1.07; P=.0006), American Society of Anesthesiologists 3 or 4 (adjusted odds ratio, 1.55; 95% confidence interval, 1.03-2.31; P=.03), and preoperative renal failure (adjusted odds ratio, 8.87; 95% confidence interval, 1.16-44.15; P=.04) remained significantly associated with developing venous thromboembolism. Neither laparoscopic repair (compared with vaginal repair) nor concurrent procedures (hysterectomy, antiincontinence procedure, vaginal mesh insertion) were found to be significantly associated with the development of venous thromboembolism. The abdominal pelvic organ prolapse repairs were associated with an increased hazard of venous thromboembolism (hazard ratio, 3.27; 95% confidence interval, 1.96-5.45; P<.0001). Venous thromboembolism development was associated with 30-day mortality, readmission, and reoperation (all P<.0001). CONCLUSION: The overall incidence of venous thromboembolism after pelvic organ prolapse repairs based on a recent, large cohort database was very low, confirming the finding in previous smaller cohort studies. The highest venous thromboembolism risk was associated with abdominal route, and more than 60% of venous thromboembolism events occurred within 10 days after surgery. Thus, focus should be placed on risk-reducing strategies in the immediate postoperative period, with greater emphasis on patients undergoing abdominal surgery.

High-Risk Pulmonary Embolism During Labor: JACC Patient Care Pathways.

While in labor, a 37-year-old woman developed acute dyspnea, hypoxemia, and tachycardia. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction, raising the suspicion of acute pulmonary embolism. The patient indeed had bilateral pulmonary embolism, necessitating percutaneous thrombectomy. Her course was complicated by another saddle pulmonary embolus, heparin-induced thrombocytopenia, and COVID-19 infection. This clinical case illustrates the importance of prompt diagnosis of acute pulmonary embolism in a peripartum female patient, the multidisciplinary approach of management, and how to approach clinical complications such as heparin-induced thrombocytopenia. Furthermore, long-term management in acute pulmonary embolism is presented.

Anticoagulation Holiday: Resumption of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Index Traumatic Intracranial Hemorrhage.

Background: The optimal time to restart direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) after traumatic intracranial hemorrhage (tICH) is unknown. Physicians must weigh the risk of recurrent hemorrhage against ischemic stroke. We investigated rates of stroke while holding anticoagulation, hemorrhage after anticoagulation resumption, and factors associated with the decision to restart anticoagulation. Methods: Patients presenting to our level I trauma center for tICH while on a DOAC for NVAF were retrospectively reviewed over 2 years. Age, sex, DOAC use, antiplatelet use, congestive heart failure, hypertension, age, diabetes, previous stroke, vascular disease, sex score for stroke risk in NVAF, injury mechanism, bleeding pattern, Injury Severity Score, use of a reversal agent, Glasgow Coma Scale at 24 hours, hemorrhage expansion, neurosurgical intervention, Morse Fall Risk, DOAC restart date, rebleed events, and ischemic stroke were recorded to study rates of recurrent hemorrhage and stroke, and factors that influenced the decision to restart anticoagulation. Results: Twenty-eight patients sustained tICH while on a DOAC. Fall was the most common mechanism (89.3%), and subdural hematoma was the predominant bleeding pattern (60.7%). Of the 25 surviving patients, 16 patients (64%) restarted a DOAC a median 29.5 days after tICH. One patient had recurrent hemorrhage after resuming anticoagulation. One patient had an embolic stroke after 118 days off anticoagulation. Age >80, Injury Severity Score ≥16, and expansion of tICH influenced the decision to indefinitely hold anticoagulation. Conclusion: The low stroke rate observed in this study suggests that holding DOACs for NVAF for 1 month is sufficient to reduce the risk of stroke after tICH. Additional data are required to determine optimal restart timing.

Prognosis in Patients With Cardiogenic Shock Who Received Temporary Mechanical Circulatory Support.

Background: Temporary mechanical circulatory support (MCS) is often used in patients with cardiogenic shock (CS), and the type of MCS may vary by cause of CS. Objectives: This study sought to describe the causes of CS in patients receiving temporary MCS, the types of MCS used, and associated mortality. Methods: This study used a nationwide Japanese database to identify patients receiving temporary MCS for CS between April 1, 2012, and March 31, 2020. Results: Of 65,837 patients, the cause of CS was acute myocardial infarction (AMI) in 77.4%, heart failure (HF) in 10.9%, valvular disease in 2.7%, fulminant myocarditis (FM) in 2.5%, arrhythmia in 4.5%, and pulmonary embolism (PE) in 2.0% of cases. The most commonly used MCS was an intra-aortic balloon pump alone in AMI (79.2%) and in HF (79.0%) and in valvular disease (66.0%), extracorporeal membrane oxygenation with intra-aortic balloon pump in FM (56.2%) and arrhythmia (43.3%), and extracorporeal membrane oxygenation alone in PE (71.5%). Overall in-hospital mortality was 32.4%; 30.0% in AMI, 32.6% in HF, 33.1% in valvular disease, 34.2% in FM, 60.9% in arrhythmia, and 59.2% in PE. Overall in-hospital mortality increased from 30.4% in 2012 to 34.1% in 2019. After adjustment, valvular disease, FM, and PE had lower in-hospital mortality than AMI: valvular disease, OR: 0.56 (95% CI: 0.50-0.64); FM: OR: 0.58 (95% CI: 0.52-0.66); PE: OR: 0.49 (95% CI: 0.43-0.56); whereas HF had similar in-hospital mortality (OR: 0.99; 95% CI: 0.92-1.05) and arrhythmia had higher in-hospital mortality (OR: 1.14; 95% CI: 1.04-1.26). Conclusions: In a Japanese national registry of patients with CS, different causes of CS were associated with different types of MCS and differences in survival.

Severe COVID-19 pneumonia leads to post-COVID-19 lung abnormalities on follow-up CT scans.

Purpose: To investigate the association of the maximal severity of pneumonia on CT scans obtained within 6-week of diagnosis with the subsequent development of post-COVID-19 lung abnormalities (Co-LA). Methods: COVID-19 patients diagnosed at our hospital between March 2020 and September 2021 were studied retrospectively. The patients were included if they had (1) at least one chest CT scan available within 6-week of diagnosis; and (2) at least one follow-up chest CT scan available ≥ 6 months after diagnosis, which were evaluated by two independent radiologists. Pneumonia Severity Categories were assigned on CT at diagnosis according to the CT patterns of pneumonia and extent as: 1) no pneumonia (Estimated Extent, 0%); 2) non-extensive pneumonia (GGO and OP, <40%); and 3) extensive pneumonia (extensive OP and DAD, >40%). Co-LA on follow-up CT scans, categorized using a 3-point Co-LA Score (0, No Co-LA; 1, Indeterminate Co-LA; and 2, Co-LA). Results: Out of 132 patients, 42 patients (32%) developed Co-LA on their follow-up CT scans 6-24 months post diagnosis. The severity of COVID-19 pneumonia was associated with Co-LA: In 47 patients with extensive pneumonia, 33 patients (70%) developed Co-LA, of whom 18 (55%) developed fibrotic Co-LA. In 52 with non-extensive pneumonia, 9 (17%) developed Co-LA: In 33 with no pneumonia, none (0%) developed Co-LA. Conclusions: Higher severity of pneumonia at diagnosis was associated with the increased risk of development of Co-LA after 6-24 months of SARS-CoV-2 infection.

The "Lollipop" During Catheter-Directed Thrombectomy: 2 Case Examples.

Intraprocedural embolization has been described as a potential complication of catheter thrombectomy for acute pulmonary embolism and may be under-recognized. We describe 2 case examples of "Lollipopping" during thrombectomy, which may be a mechanism of intraprocedural embolization and describe our treatment approach. (Level of Difficulty: Advanced.).

Isolated congenital interruption of the right interlobar pulmonary artery with unilateral interstitial lung abnormality.

We report a case of an isolated congenital interruption of the right interlobar pulmonary artery with unilateral interstitial lung abnormality. 3D-CT with enhancement showed absent right interlobar pulmonary artery without any other abnormalities of the pulmonary artery and an enlarged inferior phrenic artery. High-resolution CT demonstrated ground-glass opacities, reticular changes, and small cysts in the right middle and lower lobes, which were compatible with interstitial lung abnormality. The patient was diagnosed with an isolated congenital interruption of the right interlobar pulmonary artery since chronic pulmonary thromboembolism, structural heart disease, systemic congenital disease, and systemic vasculitis were ruled out.

McConnell's Sign Is Not Always Pulmonary Embolism: The Importance of Right Ventricular Ischemia.

McConnell's sign is a well-established, specific echocardiographic sign for acute pulmonary embolism. Multiple theories have been proposed regarding the mechanism of McConnell's sign in the context of acute pulmonary embolism. Here, we present 2 patient cases in which McConnell's sign was seen with right ventricular ischemia without pulmonary embolism. (Level of Difficulty: Beginner.).

Evidence-based perioperative diagnosis and management of pulmonary embolism: A systematic review.

Background: The diagnosis and treatment of pulmonary embolism have multi-modal approach based on specificity, sensitivity, availability of the machine, and associated risks of imaging modalities. Aim: This review aimed to provide shreds of evidence that improve perioperative diagnosis and management of suspected pulmonary embolism. Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline 2020. After a clear criteria has been established an electronic searching database was conducted using PubMed, Google Scholar, Cochrane library, and Cumulative Index of Nursing and Allied Health Literature (CINAHL), with Key search terms included:('pulmonary embolism' AND' anesthesia management ', 'anticoagulation' AND 'pulmonary embolism', 'thrombolysis 'AND 'pulmonary embolism', 'surgery' AND' pulmonary embolism'), were used to draw the evidence.The quality of literatures were categorized based on WHO 2011 level of evidence and degree of recommendation, in addition, the study is registered with research registry unique identifying number (UIN) of reviewregistry1318." and has high quality based on AMSTAR2 assessment criteria. Results: A totally of 27 articles were included [guidelines (n = 3), Cochrane (=5), systemic reviews (n = 7), meta-analyses (=2), RCT (n = 4), cohort studies (n = 3), and cross-sectional study (n = 3) and illegible articles identified from searches of the electronic databases were imported into the ENDNOTE software version X7.1 and duplicates were removed. Discussion: Currently divergent and contradictory approaches are implemented in diagnosis and management for patients suspected of pulmonary embolism. Conclusion: All perioperative patients, especially trauma victims, prostate or orthopedic surgery, malignancy, immobility, and obesity; smokers; and oral contraceptive users, antipsychotic medications are at increased risk of venous thromboembolism and need special caution during surgery and anesthesia.

Performance Status and Long-Term Outcomes in Cancer-Associated Pulmonary Embolism: Insights From the Hokusai-VTE Cancer Study.

Background: Performance status (PS) is a reliable prognostic tool for overall survival in patients with cancer-associated pulmonary embolism (PE). However, its association with venous thromboembolism (VTE) recurrence and bleeding remains unclear. Objectives: The aim of this study was to investigate whether PS at the time of PE diagnosis and its course during follow-up are linked to VTE-related outcomes. Methods: In this post hoc analysis of the Hokusai-VTE Cancer study, multivariable survival analysis was used to examine the association of PS with anticoagulation discontinuation and the composite primary outcome of VTE recurrence or major bleeding in patients with cancer-associated PE. PS was assessed using the Eastern Cooperative Oncology Group (ECOG) scale at baseline and at predefined study follow-up visits. Results: Overall, 652 patients with cancer-associated PE were included. During 12-month follow-up, PS worsened in 317 of 642 patients (49.4%) with complete ECOG data at the end of follow-up. Those with worse ECOG values over follow-up were more likely to discontinue anticoagulation for any reason apart from death (adjusted HR: 1.59; 95% CI: 1.31-1.93). The composite primary outcome occurred in 57 of 500 patients with baseline ECOG status 0 or 1 and in 32 of 152 patients with ECOG status 2 (cumulative incidence at 12 months 10.7% [95% CI: 8.2%-13.9%] vs 14.4% [95% CI: 9.7%-21.3%]). Worse ECOG values during follow-up were associated with greater risk for the composite outcome (adjusted HR: 2.13; 95% CI: 1.24-3.67). Conclusions: ECOG PS is a valuable indicator for predicting VTE-related outcomes and may inform decision making regarding anticoagulation during follow-up in patients with cancer-associated PE.

Acute Deep Vein Thrombosis in a Cyclist With Iliac Vein Compression From Psoas Muscle Hypertrophy.

A 22-year-old avid cyclist presented with 1 month of right lower extremity pain and associated swelling. Subsequent imaging demonstrated an extensive acute deep vein thrombosis (DVT) in the setting of right iliac vein compression from psoas muscle hypertrophy. We present an unusual risk factor for DVT among cyclists. (Level of Difficulty: Intermediate.).

Early bilateral pulmonary embolism in a polytrauma patient: About a case report.

Introduction: and importance: Venous thromboembolism (VTE) is a well-known complication in polytrauma patients, associated with a high rate of mortality and morbidity. Generally pulmonary embolism (PE) is most common between the fifth and seventh days following a significant trauma, and it is uncommon before the fourth day. Their management remains a challenge to physicians given the nature and risk of blood loss from the accompanying injuries must be considered while using anticoagulant therapy. Case presentation: Here we present a case of acute pulmonary embolism in a previously healthy young woman that developed two days after a traumatic brain injury (TBI) and varying degrees of additional blunt thoracic trauma. An angio CT scan was used to make the diagnosis, and the patient was given anticoagulant medication with close monitoring and satisfactory outcomes. Conclusion: Evidence suggests that early after trauma, a considerable number of trauma patients are hypercoagulable. In patients with unexplained dyspnea/hypoxia, clinicians should maintain a high index of suspicion and explore PE early after injury. In the case of traumatic brain injury patients with cerebral contusions, intraparenchymal haemorrhages, or subdural/extradural haemorrhages, the existence of post-traumatic PE adds to the problems.

Pulmonary Embolism Complicated With Cardiopulmonary Arrest Treated With Combination of Thrombolytics and Aspiration Thrombectomy.

Systemic thrombolytic therapy is frequently used in the treatment of massive pulmonary embolism. We describe a case of pulseless electrical activity arrest, refractory obstructive shock in the setting of massive pulmonary embolism despite tissue plasminogen activator that was successfully treated with catheter-directed aspiration thrombectomy. (Level of Difficulty: Intermediate.).

A Patent Foramen Ovale Grants Cardiac Output Over an Obstructive Primary Cardiac Lymphoma.

Primary cardiac lymphomas are extremely rare and involve mainly the pericardium. We present the case of a 77-year-old man with a germinal center diffuse large B-cell lymphoma causing severe right ventricular inflow obstruction. Clinical presentation of isolated dyspnea and severe desaturation and cyanosis were, otherwise, unexpected. (Level of Difficulty: Beginner.).

Electrocardiograms in Critical Care Cardiology: Is it Acute Coronary Syndrome?

Patients with critical illness may present with electrocardiogram (ECG) findings difficult for physicians to distinguish them from acute coronary syndrome. This article provides three cases of such clinical scenarios. Examples of ECGs and their clinical characteristics and significance are discussed. (Level of Difficulty: Beginner.).

The Incidence of Venous Thromboembolism in Critically Ill Patients with SARS-CoV-2 Infection Compared with Critically Ill Influenza and Community-Acquired Pneumonia Patients: A Retrospective Chart Review.

The rate of venous thromboembolism in COVID-19 patients has been reported to be 30% (deep vein thrombosis 20% and pulmonary embolism 18%). This has been shown to be higher in COVID-19 patients admitted to the ICU. Prophylactic anticoagulation may be sufficient at ward level, but not in intensive care. A retrospective chart review was undertaken in a large university hospital. The review included 276 patients from COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia groups. The timeframe included patients admitted between 23 February 2014 and 12 May 2021. Clinical characteristics, outcomes, blood results, rates of venous thromboembolism, and anticoagulation status were recorded. The incidence of venous thromboembolism in COVID-19 Wave 1, COVID-19 Wave 2, influenza, and community-acquired pneumonia was 10.91%, 13.69%, 13.33%, and 6.81%, respectively (p = 0.481). The incidence of pulmonary embolism was 7.27%, 10.95%, 3.33%, and 5.68%, respectively (p = 0.350). The incidence of deep vein thrombosis was 5.45%, 5.48%, 10.00%, and 1.14%, respectively (p = 0.117). Although most patients were prophylactically anticoagulated, venous thromboembolism still occurred. Venous thromboembolism remains an important differential to consider in critically ill COVID-19 patients. The current literature does not advise therapeutic anticoagulation for thromboprophylaxis in the ICU.

Simultaneous Real-Time Intravascular Ultrasound-Guided Transcatheter Pulmonary Embolectomy Improves Procedural Accuracy, Efficacy, and Safety.

Percutaneous catheter-directed interventions for pulmonary embolism is a rapidly evolving field. We present the first case report of simultaneous intravascular ultrasound (IVUS) use during transcatheter pulmonary embolectomy. Real-time IVUS guidance offers the advantage of better clot visualization and precise suction catheter localization while minimizing contrast medium exposure and wire exchanges. (Level of Difficulty: Advanced.).

Prevalence, Treatment, and Prognosis of Tumor Thrombi in Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown. Objectives: This study sought to assess the prevalence of TT in RCC, its current management, and its association with venous thromboembolism (VTE), arterial thromboembolism (ATE), major bleeding (MB), and mortality. Methods: Patients diagnosed with RCC between 2010 and 2019 in our hospital were included and followed from RCC diagnosis until 2 years after, or until an outcome of interest (VTE, ATE, and MB) or death occurred, depending on the analysis. Cumulative incidences were estimated with death as a competing risk. Cause-specific hazard models were used to identify predictors and the prognostic impact. Results: Of the 647 patients, 86 had a TT (prevalence 13.3%) at RCC diagnosis, of which 34 were limited to the renal vein, 37 were limited to the inferior vena cava below the diaphragm, and 15 extended above the diaphragm; 20 patients started therapeutic anticoagulation and 45 underwent thrombectomy with/without anticoagulation. During follow-up (median 24.0 [IQR: 7.0-24.0] months), 17 TT patients developed a VTE, 0 developed an ATE, and 11 developed MB. TT patients were more often diagnosed with VTE (adjusted HR: 6.61; 95% CI: 3.18-13.73) than non-TT patients, with increasing VTE risks in more proximal TT levels. TT patients receiving anticoagulation still developed VTE (HR: 0.56; 95% CI: 0.13-2.48), at the cost of more MB events (HR: 3.44; 95% CI: 0.95-12.42) compared with those without anticoagulation. Conclusions: Patients with RCC-associated TT were at high risk of developing VTE. Future studies should establish which of these patients benefit from anticoagulation therapy.