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Importance: Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients. Objective: To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient’s lifetime. Design, Setting, and Participants: Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months. Interventions: Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy. Main Outcomes and Measures: The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient’s lifetime for the primary outcome and the secondary outcome of death from any cause. Results: A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival. Conclusions and Relevance: These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF. Trial registration: ClinicalTrials.gov Identifier: NCT03036124.

Radical resection of gliomas can increase patient's survival. There is known concern, however, that aggressive tumour removal can result in neurological morbidity. The objective of the present study was to evaluate the usefulness of low magnetic field strength (0.3 Tesla) open intraoperative magnetic resonance imaging (iMRI) for complete resection of glioma with emphasis on functional outcome.From 2000 to 2004, 96 patients with intracranial gliomas underwent tumour resection with the use of iMRI in Tokyo Women's Medical University. There were 50 men and 46 women; mean age was 39 years. Tumour volume varied from 1.2 ml to 198 ml (median: 36.5 mL). Resection rate and postoperative neurological status were compared between control group (46 cases, operated on during the initial period after installation of iMRI), and study group (50 most recent cases, in whom surgery was done using established treatment algorithm and improved image quality).Overall, mean resection rate was 93%, and medial residual tumour volume was 0.17 ml. Total tumour removal was achieved in 44 cases (46%). Compared to control group, resection rate in the study group was significantly higher (91%, vs. 95%; P0.05), whereas residual tumour volume was significantly smaller (1.7 mL vs. 0.025 mL; P0.001). Nine patients in the control group (20%) and 24 in the study group (48%) experienced temporary postoperative neurological deterioration (P0.01), however, the rate of permanent morbidity evaluated 3 months after surgery did not differ significantly between the groups investigated (13% vs. 14%).Use of iMRI during surgery for intracranial gliomas permits to attain aggressive tumour resection with good functional outcome. Nevertheless, surgical experience with the iMRI system, establishment of treatment algorithm, and improvement of image quality are of paramount importance for optimal results.

Leukocytes are important in the occurrence of reperfusion injury in coronary intervention for acute myocardial infarction (AMI). This study compared reperfusion injury caused by reperfusion using leukocyte-depleted blood (LD) and that by conventional angioplasty (control) through the reperfusion phenomenon including reperfusion arrhythmia and additional ST elevation during direct percutaneous transluminal coronary angioplasty (PTCA) in 41 patients with 21 left anterior descending artery (LAD) lesions and 20 right coronary artery (RCA) lesions. LD was prepared from 20 ml of venous blood, 20 ml of mixed blood and 60 ml of arterial blood from the patients (LD group; LAD-LD: n = 10, RCA-LD: n = 10) which was passed through a leukocyte removal filter. The blood was injected from the tip of the balloon catheter at 10 ml/min during inflation for 10 min before balloon deflation. The control group (LAD-control: n = 11, RCA-control: n = 10) underwent conventional angioplasty. The appearance of reperfusion arrhythmia [atrioventricular block (AVB)II, accelerated idioventricular rhythm (AIVR), ventricular tachycardia (VT), ventricular fibrillation (Vf)] and measurements of STmax deviation before and after reperfusion, the differences of the STmax deviation (delta ST) and additional ST elevation (LAD:or = 0.5 mV increase of sigma ST in lead V1-V6, RCA:or = 0.3 mV increase of sigma ST in lead II, III and aVF) were studied. The appearance of reperfusion arrhythmias was as follows; LAD-LD: AVB 0, AIVR 1, VT 1, Vf 0, LAD-control: AVB 0, AIVR 4, VT 2, Vf 1, NS, and RCA-LD: AVB 0, AIVR 0, VT 0, Vf 0, RCA-control: AVB 2, AIVR 0, VT 1, Vf 0, NS. There was no reperfusion arrhythmia in the RCA-LD group. There was no significant difference in the appearance of reperfusion arrhythmias between the LAD-LD and LAD-control or RCA-LD and RCA-control groups. Before reperfusion the STmax deviation (mV) was LAD-LD 0.86 +/- 0.46 vs LAD-control 0.74 +/- 0.49 and RCA-LD 0.29 +/- 0.18 vs RCA-control 0.15 +/- 0.09 and after reperfusion LAD-LD 0.63 +/- 0.35 vs LAD-control 0.81 +/- 0.49 and RCA-LD 0.13 +/- 0.15 vs RCA-control 0.20 +/- 0.12, respectively. There were no significant differences between LAD-LD and LAD-control or RCA-LD and RCA-control groups. delta ST (mV) was LAD-LD 0.23 +/- 0.56 vs LAD-control 0.07 +/- 0.60, p = 0.09 and RCA-LD 0.16 +/- 0.12 vs RCA-control 0.06 +/- 0.14, p = 0.002, respectively. The number of patients with additional ST elevation soon after reperfusion was LAD-LD 3 vs LAD-control 10, p0.05 and RCA-LD 0 vs RCA-control 8, p0.001, respectively.

Effective clinical therapy to augment intestinal absorption of water and electrolytes does not exist; the gut hormone, peptide YY (PYY), is a potent proabsorptive agent in animal models. The purpose of our study was to evaluate the effects of two novel PYY analogs, BIM-43073D and BIM-43004C, on intestinal absorption. Dogs with ileal Thiry-Vella fistulae (TVF) were treated with either PYY, BIM-43073D, or BIM-43004C. Administration of BIM-43073D significantly increased water and sodium absorption over baseline and maintained this level of increased absorption for a longer duration than an equimolar dose of PYY. Administration of BIM-43004C significantly increased sodium and water absorption over baseline at a level equal to that of PYY. The novel PYY analogs, BIM-43073D and BIM-43004C, are effective proabsorptive agents with BIM-43073D producing more sustained effects than PYY. These compounds may be clinically useful in the treatment of gut malabsorption in conditions such as cholera, Crohn's disease, and the short-bowel syndrome.

Patients with laterocollis or rotatory type torticollis tend to show abnormal contraction of the levator scapulae muscle and the scalene muscles. These muscles are innervated from the anterior branches of the cervical spinal nerves. Because of this, the traditional Bertrand operation dealing with posterior branches does not adequately affect the symptoms of laterocollis. The authors report selective denervation of the levator scapulae muscle in three patients and discuss its rationale. All the three patients underwent denervation of both the C1-C6 posterior spinal rami and the branches from the C3 and C4 anterior rami to the levator scapulae muscle. We added myotomy of the scalene muscle in one patient, and denervation of the omohyoid muscle which is innervated from the ansa cervicalis and the descending branch of the hypoglossal nerve. The pre/post-operative Tsui scores were 12/4, 15/1, and 14/3 respectively. There were no complications. We conclude that selective peripheral denervation of the levator scapulae muscle is safe and effective in the treatment of laterocollic type torticollis.

The authors evaluated the results of selective peripheral denervation (SPD) of posterior rami of the cervical spinal nerves and/or the accessory nerve for spasmodic torticollis. Five patients underwent seven operations in total and the results were evaluated with the modified Tsui's score which was used in the clinical trial of botulinum toxin (BTX) for torticollis in Japan. The preoperative score was 10.8 +/- 2.2 (mean +/- S.D.) and the postoperative score was 1.4 +/- 1.7. The score changes indicated the effects of the operation as "excellent" in four cases and "good" in one case. These results indicate that SPD is superior to BTX in terms of control of symptoms in spasmodic torticollis. After the initial operation, however, two patients showed the so-called "mole-hitting game phenomenon" in which normal muscles develop abnormal contraction after denervation of abnormal muscles. This forced us to perform the second operations. Although this phenomenon was first described in botulinum toxin treatment, this is probably the first report in surgically denervated cases.

The superior septal approach (SSA) for mitral valve surgery is a useful approach, but it may bring about demage to sinus node function or an atrial electrical vulnerable condition because the sinus node artery is divided and a large portion of both atria is incised. From April 1992 to December 1994, we used this approach in 17 patients. There was no hospital death and none had perioperative complications associated with the approach. All nine patients in sinus rhythm preoperatively returned to sinus rhythm before discharge from the hospital and remained so at late follow-up. Five of 9 patients with sinus rhythm had electrophysiological examination preoperatively and all 9 patients had the examination postoperatively. Atrial vulnerability was not deteriorated after the operation in all cases. Under pharmacologic autonomic blockade, sinoatrial conduction time (SACT), sinus node recovery time (SNRT) after overdrive atrial pacing, and corrected SNRT were 73 +/- 35 msec, 1142 +/- 168 msec, and 365 +/- 122 msec, respectively. All these values were with in normal range and these were no significant differences between before and after the operation. All patients with sinus rhythm had 3 minutes of Bruce stage 1 exercise 9 months after the operation. The heart rate response to the exercise was as good as in healthy control people. In conclusion, as far as the midterm postoperative period, the effect of SSA on sinus node function and atrial vulnerability was acceptable.

We investigated the short-term effects of an intrathecal bolus injection of baclofen on central pain due to stroke or spinal cord injury. Pain relief was obtained in 64% of the patients. The effects developed 1-2 hours after the injection and continued for 10-24 hours. Both spinal segmental and supraspinal mechanisms may be involved in the production of baclofen-analgesia.

We have used an alternative technique in Total Cavopulmonary Connection without using any prosthetic material. The technique is a modification of Senning operation in which a flap of right atrial wall is used to create a tunnel between inferior vena cava and superior vena cava. We used this modified technique in two cases, and they showed excellent postoperative convalescence.

Seven patients with brain abscess underwent CT-guided stereotactic aspiration using Iseki's stereotactic apparatus. Three of them were under the age of fifteen and four were older than thirty. The lesions were single and round in four cases, multilobular in two and multiple in one patient. Operations were performed after systemic administration of antibiotics for more than two weeks and after capsule formation was confirmed on CTs. Preoperative volume of the abscesses was estimated from CTs. The target point chosen was the center of the ring of the largest diameter in the enhanced lesion. Abscess was aspirated under monitoring with intraoperative CT scan. No continuous drainage was performed and no antibiotics were given directly into the abscess cavity. In all cases the center of the abscess was punctured with a single trial. Average volume of the preoperative brain abscesses was 18.8ml. Aspirated volume at the time of the operation averaged 16.9ml and all the abscesses decreased to unmeasurable size on CTs. In five of seven patients abscesses were cured after a single aspiration, and in one case after the second operation. One case required extirpation of the lesion. During the follow-up period of four months to five and a half years six patients showed no recurrence. One patient died of unrelated cause four and a half years after the operation. No operative complication was noted. There was no operative morbidity or mortality. Using a CT guided stereotactic method, brain abscess is punctured so accurately, regardless of its location and size, that damage to the surrounding brain during operation can be minimized. Therefore it is highly possible to aspirate abscesses completely.(ABSTRACT TRUNCATED AT 250 WORDS)

The present report is concerned with the results of bilateral percutaneous high cervical cordotomy (60 patients) compared with those of unilateral cordotomy (161 patients). The result of pain relief is classified into 4 grades based on Hitchcock's criteria; grade 1: complete pain relief, grade 2: almost complete pain relief with slight residual pain, grade 3: persisting pain, but tolerable, grade 4: persisting pain, untolerable. In cases of bilateral cordotomy (60 patients), 76% of the cases showed grade 1, 19% being grade 2, 3% being grade 3 and 2% being grade 4. On the contrary, the unilateral cordotomy (161 patients) showed less impressive results, particularly in grade 1, namely, grade 1 being 64%, grade 2 being 18%, grade 3 being 14% and grade 4 being 4%. Clinically acceptable results (grade 1 plus grade 2) were, therefore, obtained in bilateral cordotomy (95%) as compared with unilateral cordotomy (82%). The difference in pain relief between bilateral and unilateral procedure observed in the present investigation is contrary to that reported previously by others. The possible explanation for less impressive result in regard to grade 1 of unilateral cordotomy is that unilateral cordotomy was performed in this series to alleviate the major side of patient's pain, followed by latent pain on the other side postoperatively, which is not uncommon phenomenon in cancer pain. Whereas all of the bilateral cordotomies were done either for midline pain or bilateral pain, unilateral cordotomy gave satisfactory pain relief in some cases of midline pain. Midline pain, therefore, does not necessarily require bilateral cordotomies from a clinical point of view.(ABSTRACT TRUNCATED AT 250 WORDS)

Late results in 139 patients undergoing open repair of tetralogy of Fallot from 1965 to December 1975 were analyzed. Their ages ranged from 1 year to 35 years. All patients were repaired through a right ventricular approach. One hundred two patients had infundibulectomy alone (non-patch group) and 14 required right ventricular outflow patch (RV-patch group) and 23 trans-annular patch. The hospital mortality rate was 18.7% (26 cases) and 103 patients were discharged and have been followed until death or for 13-24 years. Cardiac catheterizations were performed in 80 patients an average of 1.8 years after correction. Right ventricular systolic pressure was 49.8 +/- 22.4 mmHg in non-patch group, 41 +/- 16.5 mmHg in RV-patch group and 54.5 +/- 14.2 mmHg in PA-patch group. Seven in 11 patients of PA-patch group had over an 8 mmHg of right ventricular end diastolic pressure. Six patients died during the follow up: four deaths in the first 5 years, 2 between 5 and 15 years. The causes of death were congestive heart failure (3), sudden (1), pneumonia (1) and accidental (1). Late complications were 3 arrhythmias and 2 reoperations. Event free rate at 24 years was 74.8 +/- 3.8%.

The occurrence of epileptic seizures is not rare after craniotomy. The authors examined the incidence of postoperative epilepsy in 150 patients of intracranial aneurysm. Anticonvulsants were given to all patients after operation, but in 12 cases anticonvulsants were discontinued because of liver dysfunction. One hundred and eight out of 138 cases (78%) were prescribed polypharmaceutically, and 30 of 138 cases (22%) were monopharmaceutically. The daily dose of anticonvulsants was as follows; diphenylhydantoin (DPH) was 150-300 mg, phenobarbital (PB) was 50-100 mg, valproic acid (VPA) was 600-1200 mg, and carbamazepin (CBZ) was 200-600 mg. Postoperative epilepsy occurred in 14 of 150 cases (9.3%); 13 cases with anticonvulsants, and 1 case without anticonvulsants. The site of aneurysm was as follows; 6 cases (10.3%) of AC aneurysm, 3 cases (9.7%) of MC aneurysm, 1 case (2.4%) of IC aneurysm, and 4 cases (21.1%) of multiple aneurysm. The interval between operation and epileptic seizure was ranged 2 to 57 months (mean 19.8 months); in 7 cases (50%) within 1 year, and in 13 cases (93%) within 3 years. The authors emphasize that prophylactic use of anticonvulsants is effective to control subclinical epileptic seizures, prescribing anticonvulsants to all patients after craniotomy in general. The medication of anticonvulsants for 3 years would be necessary for avoiding postoperative epileptic seizure.

During the last 2 years, 46 cases of hypertensive intracerebral hemorrhage in the basal ganglia were treated by CT guided stereotactic aspiration and their outcome was evaluated in terms of the rate of hematoma removal, the change of consciousness level and the recovery of motor and sensory functions. They are aged from 45 to 79 years old, the average 56, and aspirated 1 to 24 days after the onset, two third of them being within 1 week. The whole procedure was done in the CT room under direct CT guidance and by one trial. In putaminal type hemorrhage, the removed hematoma volumes ranged from 9 to 48 ml, average being 23.7 ml, in thalamic type from 5 to 29 ml, average being 15.5 ml. The average rate of removal was 81.1% in 30 cases within 1 week. In most cases, preoperative consciousness was not severely disturbed, in putaminal type, 19 were alert or confused, 4 somnolent, 5 stuperous and in thalamic type, 6, 6, 3 respectively and 2 were semicomatous, one of them had herniation sign. In putaminal type all but 2 cases recovered to alert or confused state, the first one had postoperative bleeding and the other was already apallic preoperatively. In thalamic type, we lost 3 cases, 2 by gastrointestinal bleeding and 1 DIC, by rehemorrhage 2 months after the operation. All but one who was semicomatous preoperatively recovered to alertness. In motor function, some cases of the putaminal bleeding with intact internal capsule remained hemiplegic. On the other hand, most of the cases with partial destruction of the internal capsule on CT recovered well in both types of hematoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Ninety consecutive cases of hypertensive intracerebral haematoma were treated with CT guided stereotactic evacuation. The patients were composed of 61 males and 29 females, ranging from 42 to 87 years old. The location of haematoma was either in the putamen (59 cases) or in the thalamus (31 cases). The average volume of the evacuated haematoma was 21.4 ml in the putaminal haematoma and 14.0 ml in the thalamic haematoma. Postoperative follow-up study in 46 patients showed good recovery of neurological deficits both in putaminal and thalamic group. Criteria of surgical indication of CT-guided stereotactic evaluation of intracerebral haematoma were advocated based on the author's clinical experience.

Significance probability mapping (SPM) of brain electrical activity first described by Duffy et al. is useful tool for studying functional aspects of brain disease. Z-statistic SPM is able to identify the area of brain electrical activity deviated with statistic significance from the control group. The problem of this method is, however, that the nature of deviation, i.e., whether it is increase or decrease of electrical activity, can not be displayed. From this point of view, we attempted to use modified z-statistic method. Statistically deviated region and its nature can be clearly displayed on the same picture by analyzing EEG with this method. This method can be applied to SPM of evoked potentials. SPM is not yet complete method for the assessment of brain electrical activity, but there is much room for adopting other statistic method that is more suitable for the aim of the study. Functional aspects of the brain will be more readily clarified by the use of modified SPM and by combination with findings of CT scan, NMR and PET that can give morphological and metabolic information.

The peripheral course of the axon of the lingual proprioceptive neurons in 5 Japanese monkeys was studied by injecting HRP into the distal part of the hypoglossal nerve through the proximal stump. The present authors confirmed that the HRP-labeled cell bodies appeared ipsilaterally in the C2, C3 and C4 spinal ganglia. The afferents to the C2, C3 and C4 ganglia pass through the ansa hypoglossi and direct neuronal anastomosis existing between the first cervical nerve and the hypoglossal nerve. It was confirmed that in the Japanese monkey, having abundant muscle spindles in the tongue, the lingual proprioceptive neuron soma exist in the C2, C3 and C4 spinal ganglia, their peripheral axons passing through the ansa hypoglossi and the direct neuronal anastomosis.

Results of auditory brainstem response (ABR) and electrically elicited blink reflex (BR) recorded from 43 patients with severe brain damage within three days after the onset of illness were analyzed to assess the prognostic value of ABR and BR with respect to patient outcome evaluated by the criteria proposed by Jennett and Bond. It was possible to recognize, in recordings obtained from patients with severe brain damage, three basic patterns of BR as well as five patterns of ABR within three days after the onset. Three basic patterns of BR were composed of Type I, which closely approximated the BR of normal subjects except for moderately prolonged latency of R2, Type II, which indicated absence of bilateral R2 activities, and Type III, which showed absence of R1 as well as bilateral R2. ABRs were graded, in increasing order of abnormality, from Type I to Type V. Type I was almost normal pattern from wave I to wave V. Type II indicated prolonged latency or markedly reduced amplitude of waves IV and V. Type III showed absence of waves IV and V. Type IV had only wave I. Type V indicated absence of all waves. BR abnormalities significantly proved useful in predicting vital prognosis of the comatose patients with supratentorial lesion. In patients who had Type II of BR, additional studies of ABR enhanced the reliability of prediction of functional prognosis. On the other hand, ABR was recognized as stronger basis for predicting outcome in patients with infratentorial lesion. All patients with Type IV or Type V of ABR were expired within one month after the onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Difference in angles between horizontal section of SchaltenbrandBailey's atlas and horizontal section of CT based on Cantho-Meatal line is only 3.5 to 5.5 degrees. Therefore, the horizontal section of SchaltenbrandBailey's atlas can be utilized for analysis of the horizontal section of CT scan, because the basal ganglia are located approximately in the center of the cranial cavity. The lesions at the basal ganglia with superimposing technique utilizing the relation between horizontal section of SchaltenbrandBailey's atlas and analogue view of CT can be identified anatomically.

In order to identify the location of the electrode tip during percutaneous retrogasserian glycerol injection (PRGI), the blink reflex (DBR) following direct stimulation of the trigeminal complex (the gasserian ganglion, trigeminal rootlets, or the 3rd division of the trigeminal nerve) was obtained from 6 patients with trigeminal neuralgia. 1) The waveform of the DBR was very similar to that of the blink reflex (BR) elicited by percutaneous stimulation of the 1st division of the trigeminal nerve. However, the latency of early reflex (R1) as well as late reflex (R2) of the DBR was approximately 2 msec shorter than that of the conventional BR. 2) When the electrode tip was introduced into the gasserian ganglion, the DBR showed the largest response under the same recording condition, whereas the DBR was not recorded when the tip of the electrode was placed into either the arachnoid space or the subdural space. The each DBR response, however, showed the same configuration when the electrode tip was situated at the territory of the 1st, 2nd or 3rd division of the trigeminal nerve within the gasserian ganglion or the trigeminal cistern. 3) The DBR always appeared under the anesthesia with the intravenous administration of 10 mg diazepam and 30 mg pentazocine. 4) Based on the present study, the DBR proved to be an usuful parameter in determining whether the electrode tip is introduced into the trigeminal complex or not, particularly in the case of patients having no reliable sensory response to electrical stimulation.

The effect of long-term anticonvulsants on bone change was evaluated by microdensitometric method (MD method) in 221 outpatients of Neurological Institute Tokyo Women's Medical College. Laboratory findings including serum Ca, P, Al-p were compared with severity of bone change. Following results were obtained; In 221 patients, 159 cases (72%) were normal, 31 cases (14%) were in the initial stage of abnormality, 23 cases (10%) in grade I, 7 cases (3%) in grade II and one case (1%) in grade III of abnormality. Incidence of abnormality was high in the age of 26-35 years old and in the age over 56 years old. Total dose, serum concentration of diphenylhydantoin (DPH) as well as phenobarbital (PB) and also duration of administration of PB correlated positively with severity of bone change. Duration of administration of DPH and valproic acid (VPA), total dose and serum concentration of VPA did not correlate with severity of bone change. Serum Ca correlated with severity of bone change, but P and Al-p did not correlate with severity of bone change. Pattern of bone change was estimated by two parameters of MD method (MCI and GSmax). Results showed that most of the osteopathy (grade I-III by MD method) fell into osteoporotic type. Based on these results, it is suggested that roentgenologic and biochemical supervision of the patients is required during long-term anticonvulsant therapy.