An improved method for generating human spinal cord neural stem cells.

Neural stem cells have exhibited efficacy in pre-clinical models of spinal cord injury (SCI) and are on a translational path to human testing. We recently reported that neural stem cells must be driven to a spinal cord fate to optimize host axonal regeneration into sites of implantation in the injured spinal cord, where they subsequently form neural relays across the lesion that support significant functional improvement. We also reported methods of deriving and culturing human spinal cord neural stem cells derived from embryonic stem cells that can be sustained over serial high passage numbers in vitro, providing a potentially optimized cell source for human clinical trials. We now report further optimization of methods for deriving and sustaining cultures of human spinal cord neural stem cell lines that result in improved karyotypic stability while retaining anatomical efficacy in vivo. This development improves prospects for safe human translation.

Nationwide study of surgery for primary infected abdominal aortic and common iliac artery aneurysms.

BACKGROUND: Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy remain poorly defined. METHODS: A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR). RESULTS: Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P < 0.001). Propensity score-matched analyses demonstrated no significant differences between EVAR and in situ graft replacement in terms of 3-year all-cause and aorta-related mortality rates (P = 0.093 and P =0.472 respectively). CONCLUSION: In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.

Risk prediction model for early outcomes of revascularization for chronic limb-threatening ischaemia.

BACKGROUND: Quantifying the risks and benefits of revascularization for chronic limb-threatening ischaemia (CLTI) is important. The aim of this study was to create a risk prediction model for treatment outcomes 30 days after revascularization in patients with CLTI. METHODS: Consecutive patients with CLTI who had undergone revascularization between 2013 and 2016 were collected from the JAPAN Critical Limb Ischemia Database (JCLIMB). The cohort was divided into a development and a validation cohort. In the development cohort, multivariable risk models were constructed to predict major amputation and/or death and major adverse limb events using least absolute shrinkage and selection operator logistic regression. This developed model was applied to the validation cohort and its performance was evaluated using c-statistic and calibration plots. RESULTS: Some 2906 patients were included in the analysis. The major amputation and/or mortality rate within 30 days of arterial reconstruction was 5.0 per cent (144 of 2906), and strong predictors were abnormal white blood cell count, emergency procedure, congestive heart failure, body temperature of 38°C or above, and hemodialysis. Conversely, moderate, low or no risk in the Geriatric Nutritional Risk Index (GNRI) and ambulatory status were associated with improved results. The c-statistic value was 0.82 with high prediction accuracy. The rate of major adverse limb events was 6.4 per cent (185 of 2906), and strong predictors were abnormal white blood cell count and body temperature of 38°C or above. Moderate, low or no risk in the GNRI, and age greater than 84 years were associated with improved results. The c-statistic value was 0.79, with high prediction accuracy. CONCLUSION: This risk prediction model can help in deciding on the treatment strategy in patients with CLTI and serve as an index for evaluating the quality of each medical facility.

Risk model for severe postoperative complications after total pancreatectomy based on a nationwide clinical database.

BACKGROUND: Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications. METHODS: Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato-Biliary-Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien-Dindo grade III needing reoperation, or grade IV-V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c-statistics and a calibration plot. RESULTS: A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30-day and in-hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c-statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81). CONCLUSION: The risk model may be used to predict severe complications after total pancreatectomy.

ANTECEDENTES: La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves. MÉTODOS: Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato-Bilio-Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien-Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración. RESULTADOS: Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59-0,81). CONCLUSIÓN: El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.

Rupture of an aneurysm of a coronary arteriovenous fistula.

Coronary arteriovenous fistula is a relatively rare congenital malformation. The course of this malformation is generally benign, and rupture of the fistula is thought to be very rare. We report a case of rupture of an aneurysm of a coronary arteriovenous fistula that originated from the distal left circumflex coronary artery and drained into the right atrium; this rupture was successfully treated with an operation.

Giant pseudoaneurysm of the right sinus of Valsalva.

A pseudoaneurysm of the sinus of Valsalva is a very rare cardiac abnormality. We report a surgical case of the pseudoaneurysm of the right sinus of Valsalva in a 77-year- old woman. The histopathological examination of the resected aneurysmal wall revealed that it was a pseudoaneurysm without any specific inflammatory changes. Although we cannot identify the clear cause of the formation of the pseudoaneurysm, we believe it may have been a type of spontaneous rupture of the sinus of Valsalva.

Amlodipine is comparable to angiotensin-converting enzyme inhibitor for long-term renoprotection in hypertensive patients with renal dysfunction: a one-year, prospective, randomized study.

Unlike angiotensin converting enzyme inhibitors (ACEI), few long-term studies have shown calcium antagonists to retard the progression of renal dysfunction. Our aim was to prospectively compare the effects of amlodipine and ACEI (enalapril) on renal function in hypertensive patients with renal impairment due to chronic glomerulonephritis and essential hypertension. A total of 72 hypertensive patients with serum creatinine (Cr) > 1.5 mg/dL were randomly allocated to treatment with either drug. During a 1-year period, 33% of the patients treated with ACEI dropped out due to adverse events, whereas 9% of patients with amlodipine dropped out. Data of 28 patients were available for analysis of more than 1-year follow-up. Reductions in blood pressure were comparable between the amlodipine (from 165/101 to 138/81 mm Hg) and ACEI groups. Serum Cr increased from 2.1+/-0.8 (SD) to 2.6+/-1.0 mg/dL with amlodipine (n = 16), but the difference was equivalent to that with ACEI (n = 12). Creatinine clearance (Ccr) in the moderate dysfunction group (basal Cr, 1.5 to 2.0 mg/dL) changed from 36+/-10 to 33+/-11 mL/min (not significant) with amlodipine, and the change was similar to that noted with ACEI. Annual declines in Ccr with amlodipine (-3.7 mL/min/year) and ACEI (-2.6 mL/min/year) were comparable, and both tended to be smaller than the annual decline in glomerular filtration rate reported in the Modification of Diet in Renal Disease study (-6 mL/min/year). Serum potassium was increased significantly (P < .01), from 4.5+/-0.4 to 5.3+/-0.8 mEq/L, only in the ACEI group. This 1-year prospective study demonstrated the effect of amlodipine on renal function to be likely the same as that of ACEI. Furthermore, amlodipine was better tolerated than ACEI for hypertensive patients with renal dysfunction.

[Angiographic studies of atherosclerotic changes in coronary vein grafts after operation].

A total of 230 vein grafts were studied angiographically in 116 unselected survivors of 260 coronary bypass operations performed from May 1977 through October 1989 in order to investigate atherosclerotic changes in coronary vein grafts after operation. These patients were divided into three groups according to the interval from operation to angiography. In group A (30 patients) the interval was less than one year (mean interval 8.2 months), in group B (73 patients) from one to five years (mean interval 19.2 months) and in group C (13 patients) more than 5 years (mean interval 96.6 months). Fifty-five vein grafts were in group A, 153 vein grafts in group B and 22 vein grafts in group C. The graft patency rate of each group was 83.6%, 89.5% and 90.9% respectively (N.S.). To classify angiographic appearances we believe to be caused by atherosclerosis, we devised a grading system. Category I indicated that the graft outline was completely smooth without any irregularity; Category II indicated that less than 50% of the estimated surface area of the graft intima was irregular; Category III indicated that more than 50% of the intima was involved. Significant stenosis indicated narrowing reducing the lumen to less than 50% of the graft. Of the 203 patent grafts 181 grafts (89%) were in Category I, 22 grafts (11%) in Category II, but no graft in Category III. In group A of the 46 patent grafts 45 grafts (98%) were classified as Category I and 1 graft (2%) was classified as Category II.(ABSTRACT TRUNCATED AT 250 WORDS)

[Early and late operative results of simultaneous aortic valve and ascending aorta replacement].

Thirty-four patients of ascending aortic aneurysm associated with aortic regurgitation were treated with simultaneous aortic valve and ascending aorta replacement utilizing composite graft, until December 1990. Twenty-four patients of the group were diagnosed as Marfan's syndrome and 17 had aortic dissection. For the operative procedure, Bentall's technique were employed in 25 patients and other modifications in nine. Operative death was observed in three cases (8.8%) due to low output syndrome, caused by coronary ostium abnormality, all in Marfan's syndrome. Late death was observed in six including 2 hospital deaths of cerebro-vascular disturbance and sepsis. Other causes of death were rupture of residual aneurysm (in 3) and LOS at reoperation (in 1). Hospital survivors remarkably improved in NYHA class and in cardiac size. Actuarial survival in 3, 5, 7, and 10 years were 78%, 72%, 72%, and 62% respectively. Therefore, surgical result of composite graft technique in our institution proved to be reasonable as others. However, long term result of the procedure should be carefully evaluated, because of the anatomical and histopathological peculiarity of the disease.