Comprehensive signal detection of delirium-associated medication using the Food and Drug Administration Adverse Event Reporting System.

OBJECTIVE: Several medications are associated with delirium; however, studies with adequate statistical power are limited, and it is difficult to determine the effects of the various concomitant medications used in clinical practice. Therefore, in this study, we aimed to comprehensively evaluate the safety signals of delirium-associated drugs using a spontaneous adverse event reporting system. METHOD: The JAPIC AERS (Food and Drug Administration Adverse Event Reporting System pre-processed by the Japan Pharmaceutical Information Center) was used for the analysis in this pharmacovigilance study. The reporting odds ratio (ROR) for delirium was adjusted for using multivariate logistic regression analysis with sex, age, indication, and melatonin receptor agonist use, and 22 drug categories were targeted as covariates. RESULTS: After excluding patients with missing information, 7,527,568 patients were included in the study. Delirium signals were detected even after adjusting for covariates in 17 drug categories, including benzodiazepines (adjusted ROR, 1.76; 95% confidence interval [CI], 1.64-1.89), opioids (adjusted ROR, 4.42; 95% CI, 4.21-4.64), and tricyclic antidepressants (adjusted ROR, 2.44; 95% CI, 2.20-2.71). CONCLUSIONS: These findings suggest that many drug classes, such as benzodiazepines, are independent risk factors for delirium and strengthen the evidence of an association between delirium and medications.

Recurrent left ventricular thrombus due to essential thrombocythemia complicated by COVID-19.

Essential thrombocythemia is a risk factor for thrombosis and hemorrhage. During the perioperative period of cardiac surgery, the risk of thrombosis and hemorrhage increases. Coronavirus disease 2019 (COVID-19) is also associated with thrombosis. We present the case of a 69-year-old man with essential thrombocythemia complicated by COVID-19 who developed a left ventricular thrombus. We performed thrombectomy, but the patient developed recurrent left ventricular thrombus 8 days after surgery. Emergency redo thrombectomy was performed followed by aggressive blood-thinning therapy. The postoperative course was complicated by cardiac tamponade requiring surgical drainage 8 days after the second surgery. The patient was discharged home 25 days after the second operation without any complications. Learning objective: Left ventricular thrombus is a rare but fatal complication associated with essential thrombocythemia. COVID-19 has also been reported to cause coagulopathy. This case suggested that after surgery for left ventricular thrombus complicated by multiple risk factors including essential thrombocythemia and COVID-19, aggressive blood-thinning therapy with combination of anticoagulation, antiplatelet, and metabolic antagonist may help prevent recurrent thrombosis.

Chiral Silver Complex-Catalyzed Asymmetric Conjugate Addition of 1-Pyrroline-5-Carbonitrile to α-Enones.

The conjugated addition reaction of 1-pyrroline-5-carbonitrile to α-enones was effectively catalyzed by AgF/ThioClickFerrophos (TCF) in diethyl ether in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and nearly single diastereomers of adducts with good enantiomeric excesses (up to 97% ee) were obtained in high yields. The reduction of the nitrile group with H2/Raney Ni in ethanol successfully transformed the conjugate adduct to the corresponding spirocyclic piperidine (60% yield) as a single stereoisomer.

Acute Kidney Injury after High-Flow Regional Cerebral Perfusion in Neonatal and Infant Aortic Arch Repair.

OBJECTIVES: We applied high-flow regional cerebral perfusion (HFRCP) for aortic arch reconstruction in neonates and infants by monitoring regional oxygen saturation of the thigh (rSO2T) using near-infrared spectroscopy to maintain peripheral perfusion. This study was designed to investigate the optimal perfusion flow of HFRCP for renal protection. METHODS: From 2009 to 2021, 28 consecutive neonates and infants who underwent aortic arch reconstruction with HFRCP were enrolled. The median age of the patients was 27 days; the median body weight was 3.0 kg. In HFRCP, perfusion flow was targeted at approximately 80-100 mL/kg/min and then lowered corresponding to brain rSO2 levels and blood gas data. Isosorbide dinitrate and chlorpromazine were administered to enhance peripheral perfusion flow. Regional oxygen saturation of the forehead and thighs were monitored. The stage of acute kidney injury (AKI) was classified based on the Kidney Disease Improving Global Outcomes criteria. RESULTS: No patients had neurological events and peritoneal dialysis after surgery. The incidence of AKI was 39.3% with only three patients having greater than stage 2 AKI. The maximum postoperative serum creatinine concentration was negatively associated with the lowest rSO2T during HFRCP. The rSO2T during HFRCP was a predictive factor for postoperative creatinine increase of ≧0.3 mg/dL. The area under receiver operating characteristic curve was 0.78 with the cutoff value of 48% for rSO2T. CONCLUSIONS: The rSO2T during HFRCP is a potential predictor of postoperative renal function. To prevent AKI, the rSO2T should be preserved more than 48% by increasing HFRCP flow.

Outcomes after Rivaroxaban Treatment of Extensive Deep Vein Thrombosis.

BACKGROUND: Regression of thrombus in response to treatment with direct oral anticoagulants (DOACs) in patients with extensive deep vein thrombosis (DVT) has not been fully evaluated. This study aimed to determine the therapeutic efficacy of rivaroxaban in the treatment of extensive DVT. METHODS: We retrospectively evaluated 76 patients treated with rivaroxaban among 728 new DVT patients, at our hospital from January 2018 to March 2021. Extensive DVT was defined as thrombus connecting to 2 or more segments of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. Localized DVT was defined as a thrombus confined to 1 segment of the inferior vena cava (IVC), iliac vein, femoral vein, or popliteal vein. We compared the changes in thrombus between the extensive DVT group (36 patients) and the localized DVT group (40 patients). RESULTS: In the localized DVT group, 14 (37%) had total recanalization within 3 weeks after DOAC initiation, and 30 (79%) had total recanalization within 3 months. In the extensive DVT group, only 3 (9%) had total recanalization within 3 weeks after starting DOAC, and even after 3 months, only 5 (15%) had total recanalization. Symptoms (P = 0.01) and extensive DVT (P < 0.01) were significantly associated with the risk for failure of total recanalization. CONCLUSIONS: Rivaroxaban was highly effective for total recanalization of localized DVT but not for symptomatic or extensive DVT. In patients with symptomatic extensive DVT, catheter-based thrombolysis may be considered in selected cases.

Gluteal Blood Flow Monitoring in Endovascular Aneurysm Repair With Internal Iliac Artery Embolization.

BACKGROUND: When an internal iliac artery (IIA) has to be embolized during endovascular aneurysm repair (EVAR), buttock claudication sometimes poses problems. However, there is no established method to evaluate intraoperative blood flow to the gluteal muscles.Methods and Results:Gluteal regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy (NIRS) during surgery, and changes in rSO2were compared with treatment results. Twenty-seven patients who underwent EVAR and IIA embolization at our institution between April 2019 and May 2020 were included in this study. The association between intraoperative changes in rSO2and postoperative incidence of buttock claudication was analyzed. Furthermore, the presence or absence of communication between the superior and inferior gluteal arteries and the intraoperative changes in rSO2were compared to ascertain whether rSO2reflects blood flow change. Postoperative buttock claudication occurred in 4 of 19 patients (21%) with unilateral occlusion of IIA and in 4 of 8 patients (50%) with bilateral occlusion of IIAs. rSO2was found to decrease significantly further in patients with buttock claudication than in patients without buttock claudication (-15±12% vs. -4±16%, P<0.05). In addition, rSO2was predominantly lower in patients without the communication between the superior and inferior gluteal arteries than in those with the communication. CONCLUSIONS: Gluteal rSO2is useful as an indicator of intraoperative gluteal blood flow.

Risk Factors for Progression of Distal Deep Vein Thrombosis.

BACKGROUND: There is insufficient evidence regarding the optimal treatment method for distal deep vein thrombosis (DVT), including indications for anticoagulation therapy. Treatment results of patients with distal DVT were evaluated to clarify the risk factors that result in extension of distal DVT to the proximal vein and indications for anticoagulation therapy.Methods and Results:Among 430 patients with DVT between January 2018 and December 2019, 253 were diagnosed with distal DVT; 41 patients who had already started anticoagulation therapy were excluded, and the remaining 212 were included as study subjects. Anticoagulation therapy was not started immediately; conservative treatment with compression stockings was performed. Ultrasonography after 2 weeks revealed thrombus disappearance in 39 patients (21%), and thrombus reduction in 38 patients (20%). In contrast, extension of thrombus to the proximal vein was noted in 12 patients (6.3%) and anticoagulation therapy was commenced. After 3 months, the thrombus had disappeared in 75 patients (52%). No patient developed pulmonary thromboembolism during follow-up. With respect to the risk factors for extension to proximal vein during conservative treatment, active cancer (P=0.03), prolonged bed rest (P<0.01), and D-dimer level >8µg/mL (P=0.01) were identified. CONCLUSIONS: It is reasonable to consider anticoagulation therapy in distal DVT patients with active cancer, prolonged bed rest or high D-dimer level.

Watch-and-wait strategy for type A intramural haematoma and acute aortic dissection with thrombosed false lumen of the ascending aorta: a Japanese single-centre experience.

OBJECTIVES: In this study, we investigated the early and midterm outcomes of initial watch-and-wait strategy for Stanford type A intramural haematoma and acute aortic dissection with thrombosed false lumen of the ascending aorta in patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection in the ascending aorta. METHODS: Inpatient and outpatient records were retrospectively reviewed. RESULTS: Of the 81 patients with type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta between April 2011 and April 2019, a watch-and-wait strategy was selected in 46 patients. The mean age of the patients was 68 years, and 22 (48%) patients were female. Ten patients underwent emergency pericardial drainage for cardiac tamponade at the time of presentation and 8 patients underwent aortic repair during hospitalization for new ulcer-like projection, re-dissection or rupture. In-hospital mortality occurred in 2 (4%) patients. During follow-up, survival at 1 and 2 years was 95% and 92%, respectively. There was no significant difference in survival or aortic events between patients in whom the watch-and-wait strategy and emergency surgical treatment were indicated. CONCLUSIONS: The early and midterm outcomes of the initial watch-and-wait strategy were favourable for type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta in Japanese patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection. Further study is required to show the safety of this strategy.

Repeat surgical intervention after aortic repair for acute Stanford type A dissection.

OBJECTIVE: This study aimed to evaluate the outcomes of repeat interventions on the aorta and aortic valve after surgery for acute Stanford type A aortic dissection. METHODS: The hospital records of patients who underwent repeat surgical intervention between April 2011 and March 2017 for late complications after acute type A aortic dissection repair were retrospectively reviewed. RESULTS: We identified 17 patients with mean age of 62 ± 8 years; 13 were men. The mean interval from the initial emergency aortic repair to the repeat intervention was 5.8 ± 5.4 years (range 133 days-16.6 years). Ten patients had dilatation or rupture of the residual type B aortic dissection; six of them had retrograde type A aortic dissection at the onset and did not undergo resection of the primary entry. Five patients had a pseudoaneurysm at the anastomosis; four of them were receiving anticoagulation medication. Three patients had aortic regurgitation; two of them were associated with the gelatin-resorcinol-formaldehyde glue that was used during the initial surgery. There was no early mortality after repeat intervention and no late death after a mean follow-up period of 3.3 ± 2.0 years. CONCLUSIONS: Repeat surgical intervention on the aorta and aortic valve after repair of acute type A aortic dissection had favorable early and mid-term outcomes and was not associated with early or late death. Long-term follow-up with imaging and echocardiography was considered to be essential for early detection of residual type B dilatation, anastomotic pseudoaneurysm, and aortic regurgitation after initial aortic repair.

Norwood Procedure Performed on a Patient With Trisomy 13.

Trisomy 13 is associated with a variety of congenital anomalies, some of which are life-threatening and related to poor prognosis. Therefore, cardiac surgery is rarely offered to these patients, especially to those with complex cardiac anomalies. We report the case of a neonate weighing 2324 g who was born with severe congenital heart defects. Transthoracic echocardiography revealed the diagnoses of asplenia, single ventricle, aortic stenosis, coarctation of the aorta, hypoplastic aortic arch, and total anomalous pulmonary venous return. She was hemodynamically unstable. Palliative Norwood procedure with right ventricle-pulmonary artery conduit (RV-PA conduit) was performed at the age of 1 day to save her life. On postoperative day 7, chromosome analysis revealed trisomy 13. Echocardiography revealed good heart function; stable hemodynamic status was achieved with minimal amounts of inotropic agents. However, she developed anuria, which did not improve despite situational possible interventions, including peritoneal dialysis and continuous hemodiafiltration. On postoperative day 37, she succumbed to sudden cardiorespiratory failure. Nevertheless, this case indicates that a neonate with trisomy 13 can have a better chance at survival with cardiac surgery such as the Norwood procedure with an RV-PA conduit.

Impact of the entry site on late outcome in acute Stanford type B aortic dissection†.

OBJECTIVES: This study aimed to investigate whether the entry site of acute type B aortic dissection affects late outcomes. METHODS: Inpatient and outpatient records were retrospectively reviewed. RESULTS: We identified 224 cases of acute type B aortic dissection between 1998 and 2013. Of these 224 patients, 168 were men and the age was 64.2 ± 12.6 (range 23-94) years, from which 130 presented with the entry at a location downstream of the distal aortic arch, 67 with the entry at the outer curvature of the distal aortic arch and 27 with the entry at the inner curvature. At the initial presentation, 127 patients had descending false lumen thrombosis. The 30-day mortality rate was 2%, and 8% of patients had malperfusion. The entry at the outer curvature was associated with a higher risk of 30-day mortality. Patients with the entry at a location downstream were significantly older, and had a higher chance for primarily thrombosed descending false lumen and a lower risk of malperfusion. At follow-up (6.0 ± 4.1 years), the actuarial survival rates were 97, 83 and 60%, freedoms from open aortic surgery were 96, 91 and 86%, aortic intervention were 73, 66 and 63% and aortic events were 71, 60 and 52% at 1, 5 and 10 years, respectively. Multivariate logistic regression analysis revealed that the outer curvature entry and maximum aortic diameter were correlated with open aortic surgery, aortic intervention and aortic events. Of the 127 patients with primarily thrombosed false lumen, the outer curvature entry was significantly correlated with aortic events. CONCLUSIONS: The primary entry at the outer curvature of the distal aortic arch, as well as the large aortic diameter, is associated with a higher risk of late open aortic surgery, aortic intervention and aortic events in acute type B aortic dissection. Thus, the entry site should be taken into consideration in the establishment of an appropriate treatment indication of type B aortic dissection.

Seventeen-month-long paracorporeal biventricular mechanical support as a bridge to transplantation for severe dilated cardiomyopathy.

The long-term management of paracorporeal biventricular assist devices (BiVAD) is difficult because of significant risks of bleeding, thrombosis, and infection. Here we report the case of a 41-year-old woman with severe dilated cardiomyopathy who developed serious cerebral bleeding after receiving a paracorporeal BiVAD but recovered well after treatment. She eventually underwent cardiac transplantation 17 months after implantation of the paracorporeal BiVAD.

Elephant trunk in a small-calibre true lumen for chronic aortic dissection: cause of haemolytic anaemia?

OBJECTIVES: The elephant trunk technique for aortic dissection is useful for reducing false lumen pressure; however, a folded vascular prosthesis inside the aorta can cause haemolysis. The purpose of this study was to investigate whether an elephant trunk in a small-calibre lumen can cause haemolysis. METHODS: Inpatient and outpatient records were retrospectively reviewed. RESULTS: Two cases of haemolytic anaemia after aortic surgery using the elephant trunk technique were identified from 2011 to 2013. A 64-year-old man, who underwent graft replacement of the ascending aorta for acute Stanford type A aortic dissection, presented with enlargement of the chronic dissection of the descending aorta and moderate aortic regurgitation. A two-stage surgery was scheduled. Total arch replacement with an elephant trunk in the true lumen and concomitant aortic valve replacement were performed. Postoperatively, he developed severe haemolytic anaemia because of the folded elephant trunk. The anaemia improved after the second surgery, including graft replacement of the descending aorta. Similarly, a 61-year-old man, who underwent total arch replacement for acute Stanford type A aortic dissection, presented with enlargement of the chronic dissection of the descending aorta. Graft replacement of the descending aorta with an elephant trunk inserted into the true lumen was performed. The patient postoperatively developed haemolytic anaemia because of the folded elephant trunk, which improved after additional stent grafting into the elephant trunk. CONCLUSIONS: A folded elephant trunk in a small-calibre lumen can cause haemolysis. Therefore, inserting an elephant trunk in a small-calibre true lumen during surgery for chronic aortic dissection should be avoided.

Key success factors for thoracic endovascular aortic repair for non-acute Stanford type B aortic dissection.

OBJECTIVES: We aimed to determine the key factors associated with successful early and late outcomes after thoracic endovascular aortic repair (TEVAR) for non-acute Stanford type B aortic dissection at our institution. METHODS: Inpatient and outpatient records were retrospectively reviewed. Patients operated on within 14 days after the onset of acute aortic dissection and those with rupture or malperfusion were excluded. RESULTS: Forty-five patients (mean age, 55.5 ± 13.1 years; 23-79 years) underwent 53 TEVAR operations for non-acute Stanford type B aortic dissection between 1998 and 2012. Thirty-four patients had a patent false lumen and 19 had an ulcer-like projection (ULP). No early mortality was observed. At late follow-up (7.5 ± 3.9 years) of the 45 patients, survival after the initial TEVAR was 100, 86 and 63%; freedom from aortic reintervention was 87, 73 and 59%; and freedom from open aortic surgery was 89, 84 and 73%, at 1, 5 and 10 years, respectively. Of 15 late deaths, 2 were due to aortic rupture and 2 were operative deaths associated with aortic surgery. Of the 34 patients with patent false lumens before TEVAR, 25 had their descending false lumens thrombosed; of these 25, 16 had remodelling of the descending aorta; and of these 16, 4 had complete obliteration of the false lumen of the entire aorta. By bivariate analysis, the site of the primary entry and age were significantly associated with thrombosis of the descending false lumen, maximum aortic diameter was associated with remodelling of the descending aorta, and absence of abdominal branches arising from the false lumen was associated with complete obliteration of the false lumen of the entire aorta. CONCLUSIONS: The early results of TEVAR for non-acute Stanford type B aortic dissection were favourable. However, for cases with patent false lumens, complete obliteration of the false lumen of the entire aorta was difficult to achieve. Absence of the primary entry at the outer curvature of the distal aortic arch, younger age, small aortic diameter and absence of the abdominal aortic branches arising from the false lumen were the key success factors.