A 73-year-old man who underwent redo aortic valve replacement due to dysfunction of tissue heart valve developed hypoxemia with bilateral infiltrates on frontal chest radiograph and hypotension shortly after his operation. Due to the presence of progressive hypotension and hypoxemia, we inserted an intra-aortic balloon pump and, furthermore, provided percutaneous cardiopulmonary support. We ruled out cardiogenic pulmonary edema based on information from various examinations, including echocardiography, and subsequently diagnosed possible transfusion-related acute lung injury (possible TRALI). The patient was treated by mechanical ventilation and circulatory support under close supervision, showing a trend of improvement from postoperative day 2 and discontinuing mechanical ventilation on postoperative day 11. The patient made an uneventful recovery and was discharged on postoperative day 50. Cardiac surgery patients are at particular risk for TRALI, so physicians should consider TRALI whenever a patient develops hypoxemia during or shortly after transfusion. Rapid diagnosis and appropriate treatment of TRALI are especially important in cardiac surgery patients.

Renal function, hemolysis and hematologic parameters after transfusion using a cell-separation (CS) device were retrospectively evaluated during abdominal aortic aneurysm repair. Fifty-eight patients were divided into two groups, that is, the CS group (n=39) who received autologous retransfusion using the CS device and the non-CS group (n=19) who were operated before 1989, when we started to use CS device in our operating theater. Hematologic parameters and levels of GOT, GPT, LDH, BUN and creatinine were assessed before and 1, 2, 3, 4 and 7 days after the operation. Mean transfused homologous blood was 1.3±1.8 units in the CS groups and 4.9±3.1 units in the non-CS group (p<0.05). Peak levels of LDH and GPT were significantly higher in the CS group than the non-CS group (p<0.05) after the operation (GOT, CS group: 60.4±29.1IU/l vs non-CS group: 34.8±12.3IU/l, LDH, CS group: 643±324IU/l vs non-CS group: 446±108IU/l). There was no significant difference in the levels of BUN and creatinine levels between the two groups. Hemoglobin levels decreased gradually after the operation in CS group patients who did not receive a homologous blood transfusion. These data suggested that mild hemolysis occurred after retransfusion of autologous blood, but that the hemolysis due to the CS device had no effect on the renal function of the patients.

Objective: The aim of this study was to analyze the factors influencing the addition of clinically significant adverse reactions (CSDR) section in drug package inserts in Japan.
Methods: The summaries of investigation results from August 2011 to July 2014 were evaluated.  The revisions were classified into revisions based only on case reports from Japan ([Revision Y]) and revisions based on other information and/or case reports from Japan ([Revision X]).  The revisions were classified into MedDRA system organ class (SOC).  As index of amount of information from domestic case reports, the number of accumulated cases ([Case A]), cases for which a causal relationship to the product could not be ruled out ([Case B]), and fatal cases ([Case C]) were used.  In each SOC, as index of causal relationship to the product, [Index B/A] ([Case B]/[Case A]) was calculated.  Relationship of [Index B/A] to [Revision X]/all revisions, or to the number of [Case A] in [Revision Y] were evaluated.  Deference of drug lag between [Revision X] and [Revision Y] was evaluated.
Results: Three hundreds twenty-three revisions with respect to the addition of CSDR section were identified.  [Revision Y] was 203 revisions (63%).  The number of [Case A], ([Case B], and ([Case C]) that were required for [Revision X] (120 revisions) were significantly lower than that were required for [Revision Y] (p<0.0001 for all comparisons).  [Index B/A] tended to inversely correlate with [Revision X]/all revisions (r=−0.52, p=0.066), and the number of [Case A] in [Revision Y] (r=−0.61, p=0.025).  Drug lag of [Revision X] was significantly longer than that of [Revision Y] (p<0.001).
Conclusions: In future, it would especially needed to pay attention to adverse reactions with a low [Index B/A] of which revisions relatively depend on other information.

A 52-year-old woman who had been treated for miliary pulmonary tuber culosis complained of left flank pain. Abdominal aortic angiography revealed a saccular type aneurysm in the supra-renal abdominal aorta. We resected the aneurysm and reconstructed the aorta by arificial graft patch under partial extracorporeal circulation. The left renal artery was reconstructed by an artificial graft. During the operation, the superior mesenteric artery and the bilateral renal arteries were perfused by blood from the extracorporeal circuit. On pathological examination, it was shown that the aneurysm was caused by tuberculosis.

It has often been pointed out that introduction of early rehabilitation programs may convey a considerable risk of cerebral hypoperfusion, presumably due to dysautoregulation. Cerebral blood flow (CBF) was measured in six patients with cerebrovascular disease using ^99mTc-hexamethyl propyleneamine oxime single photon emission computed tomography (99^mTc-HM-PAO-SPECT) to investigate whether warm bathing with CO₂ bubble stimulation (CO₂ bathing) can be applied to early rehabilitation programs. The subjects comprised two patients with hypertensive cerebral hemorrhage, two with aneurysmal subarachnoid hemorrhage, and two with cerebral infarction. CO₂ bubble stimulation was produced by dissolving 100g of commercially available CO₂ bubble forming tablets in 300L of warm water (41°C) and a course consisting of 10 minutes of CO₂ bathing was applied for seven days. Vital signs such as blood pressure, pulse rate, and body temperatures at the axilla and the external auditory canal adjacent to the ear drum were checked during each bathing. CBF measurements and routine laboratory examinations were made before and after the seven-day course of CO₂ bathing. Student-t test was used for statistical analysis.
No definite changes were shown in vital signs before and after CO₂ bathing. A significant decrease in WBC counts was observed after CO₂ bathing, but there were no changes in values of C-reactive protein. Although no significant changes in hemisphere CBF were identified, actual values of regional CBF in the unaffected hemisphere tended to increase in two patients.
These results suggest that CO₂ bathing produces no adverse effects on cerebral perfusion and can be applied safely to early rehabilitation programs.

We performed entry closure for the chronic type B dissecting aneurysms by open surgical procedure or endovascular stent-graft placement. The purpose of this study is to evaluate the mid-term results of these patients with respect to mortality, morbidity, change of aneurysm diameter and outcome of the false lumen. From 1996 to 2003, entry closure was performed on 8 patients with chronic dissecting aortic aneurysm with an entry site in the descending aorta and visceral arteries that originated from the true lumen. The study population consisted of 4 men and 4 women with a mean age of 63.8±10.9 years. One patient had a DeBakey type III a and 7 patients had a DeBakey type III b dissecting aneurysm. Five patients underwent surgical entry closure and 3 patients underwent endovascular stent-graft placement. The mean follow-up period was 40±29 months. No operative mortalities, complications of paraplegia or visceral ischemia occurred. A leak was identified in 3 patients, 1 patient underwent an open repair with descending aortic replacement and 1 patient required additional stent-grafting. In the follow-up period, 1 patient died of cancer, but there were no dissection-related mortalities or re-operations for increase in size. With the exception of 1 case with a graft replacement, complete thrombosis of the thoracic aortic false lumen was achieved in 6 cases. There were no significant differences in the pre- and postoperative aortic diameter. Overall, complete thrombosis of the thoracic aortic false lumen was achieved with a high rate of success without a dissection-related mortality. Long-term follow-up, however, is necessary because a reduction in size did not occur in some cases.

The Japanese Ministry of Health, Labor, and Welfare lists interstitial lung disease as an serious adverse drug event.  The Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases are available to detect adverse events signals.  We analyzed reports of interstitial lung disease in FAERS and JADER and calculated the reporting fraction and reporting odds ratio (ROR) of drugs potentially associated with interstitial lung disease.  We applied Weibull shape parameter to time-to-event data in JADER.  We found FAERS to contain 3,522,995 reports from January 2004 to March 2013 and JADER to contain 292,720 reports from April 2004 to November 2013.  In FAERS, the reporting fractions of interstitial lung disease for Gefitinib, Bleomycin, and Amiodarone were 7.4% (285/3,856 reports), 3.2% (86/2,663 reports), and 1.9% (357/18,366 reports), and RORs (95% confidence interval [CI]) were 29.26 (25.89-33.07), 11.99 (9.66-14.88), and 7.29 (6.55-8.11), respectively.  In JADER, the reporting fractions of interstitial lung disease for Gefitinib, Bleomycin, and Amiodarone were 45.6% (1,070/2,348 reports), 22.1% (77/348 reports), and 27.9% (468/1,678 reports), and RORs (95% CI) were 18.46 (16.99-20.06), 5.83 (4.52-7.51), and 8.14 (7.31-9.07), respectively.  Adverse event signals of interstitial lung disease were observed in most drugs, which are warned as a suspected drug in the literature.  With the time-to-event analysis using Weibull shape parameter, time-dependency of adverse events in each drug was different.  Therefore, these drugs should be used carefully in clinical practice.

We evaluated the efficacy of evoked spinal potential (ESP) monitoring during thoracoabdominal aortic replacement to prevent intra-operative spinal ischemia. Nine patients underwent intraoperative ESP monitoring. The ESP was unchanged in 5 patients and decreased in 4 patients. However, ESP recovered in 2 of them by the following techniques: (1) perfusion of intercostal arteries, (2) elevation of distal bypass perfusion pressure, (3) slight hypothermia. Postoperative paraplegia occurred only 1 patient of the 2 whose ESP was not restored. The sensitivity and specificity of the efficacy of ESP monitoring were 100% and 87.5%, respectively. We concluded that ESP is the most useful monitoring for prevention of operative spinal ischemia during thoracoabdominal aortic replacement.

Although the pressure gradient (PG) and the effective orifice area (EOA) have been used as indices of prosthetic valve function, these values show correctly neither energy loss, nor increased workload. This study aimed to evaluate the prosthetic valve function using echocardiography and PG, EOA and energy loss index, a new index advocated by Garcia et al. These were calculated for 40 patients with aortic prosthetic valve replacement by SJM valve (19HP, 6 cases; 21mm, 16 cases; 23mm, 14 cases; 25mm, 4 cases). Preoperative and postoperative echocardiographic measurements and their variations were analyzed and compared according to the size of implanted valve. In the comparison before and after aortic valve replacement, left ventricular mass (383±151g vs 288±113g, p<0.01), SV1+RV5 on ECG (5.07±1.73mV vs 3.83±1.5mV, p<0.01), and diastolic left ventricular posterior wall thickness (14.4±3.7mm vs 12.9±2.8mm, p<0.05) decreased significantly after the operation. However, there was no significant difference according to the size of the prosthetic valve in these reduction rates caluculated by (preoperative value-postoperative value)/preoperative value. Small size prosthetic valves were used for patients with small diameter of left ventricular outflow tract (LVOT) (19HP, 18±2mm; 21mm, 21±2mm; 23mm, 23±4mm; 25mm, 27±3mm; p<0.01) and small body surface area (19HP, 1.5±0.2m²; 21mm, 1.5±0.2m²; 23mm, 1.7±0.1m²; 25mm, 1.8±0.1m²; p<0.01) in our study. There was a signifcant difference in EOA (19HP, 1.2±0.4cm²; 21mm, 1.9±0.7cm²; 23mm, 2.2±0.9cm²; 25mm, 3.5±1.1cm²; p<0.01), but not in ELI (19HP, 1.01±0.41cm²/m²; 21mm, 1.87±1.03cm²/m²; 23mm, 1.83±1.09cm²/m²; 25mm, 3.08±1.21cm²/m²; p=0.055) according to the size of the prosthetic valve. Small size prosthetic valves had small EOA, but showed satisfactory valve function in decreasing left ventricular hypertrophy and reducing LVM and ELI of small size was similar to that of large size.

There have been concerns that neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) cause neuropsychiatric adverse events (NPAEs).  We evaluated the number of relevant reports, reporting ratio, and reporting odds ratio (ROR) by using spontaneous reporting database, such as the Japanese Adverse Drug Event Report (JADER) (April 2004 to July 2014).  The RORs of oseltamivir, zanamivir, laninamivir, and peramivir were 11.8 (95% confidence interval (CI), 10.8-13.0), 47.0 (95% CI, 40.0-55.3), 9.5 (95% CI, 6.8-13.2), and 3.3 (95% CI, 2.1-5.1), respectively.  The lower limit of the ROR 95% CI of NPAEs of all neuraminidase inhibitors was ≥1.  We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model.  The adjusted ROR of NPAEs was 66.9 (95% CI, 50.3-88.9) in male patients treated with osletamivir aged 10-19 years.  The adjusted RORs of NPAEs were increased in male and female patients under the age of 20 years.  Neuraminidase inhibitors including oseltamivir treatment could be associated with NPAEs.  Therefore, these drugs should be used carefully in clinical practice.