A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.

Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.

Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

Successful Double-Catheter Coil Embolization of an Iatrogenic Subclavian Artery to Internal Jugular Vein Fistula After Minimally Invasive Cardiac Surgery.

It is essential to establish cardiopulmonary bypass by percutaneous insertion of a large-bore catheter via both the femoral vein and internal jugular vein (IJV) for minimally invasive cardiac surgery (MICS). Complications associated with IJV catheterization during MICS have been reported in the literature; however, vascular injury of the subclavian artery (SCA) is rare. We herein present a rare case in which an iatrogenic arteriovenous fistula (AVF) between the right SCA and IJV after MICS was successfully treated by endovascular coil embolization. A 61-year-old man who had undergone mitral valve repair by MICS 10 months before presentation was referred because of pulsatile cervical bruit and tinnitus. Radiographic examination revealed a right SCA pseudoaneurysm associated with an AVF located between the right common carotid artery and vertebral artery. The AVF was completely occluded with detachable coils using a double-catheter technique to avoid coil migration into the IJV. This technique has been used to treat high-flow or complex AVFs, including pulmonary and renal AVFs. As shown in the present case, it is also useful to treat an iatrogenic AVF between the SCA and IJV.

Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.

BACKGROUND: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. METHODS: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. RESULTS: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. CONCLUSIONS: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

Total arch replacement via antero-lateral thoracotomy with partial sternotomy in patients with a tracheostoma: report of two cases.

Midsternotomy in patients with a coexisting tracheostomy is associated with a risk of deep sternal wound infection (DSWI) or mediastinitis. We herein present two cases of total arch replacement using a surgical technique designed to avoid the danger of DSWI. Total arch replacement via an antero-lateral thoracotomy with partial sternotomy can be one of the options for patients with a tracheostoma or after laryngectomy, and can both protect organs and avoid DSWI.

Risk factors for chronic kidney disease progression over 20 years for primary prevention in Japanese individuals at a preventive medicine research center: Focus on the influence of plasma glucose levels.

AIMS/INTRODUCTION: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. MATERIALS AND METHODS: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis. RESULTS: During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). CONCLUSIONS: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part II: OCD and PTSD.

AIM: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008. METHOD: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments. RESULT: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option. CONCLUSION: OCD and PTSD can be effectively treated with CBT and medications.

Thyroid crisis mimicking clinically mild encephalitis/encephalopathy with a reversible splenial lesion: A pediatric case report.

BACKGROUND: Reversible lesions in the splenium of the corpus callosum (SCC) with viral infections are associated mainly with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We report a pediatric patient in thyroid crisis with reversible SCC lesions. CASE DESCRIPTION: We diagnosed a 9-year-old girl with thyroid crisis. She had presented with fever, tachycardia, and impaired consciousness. Magnetic resonance imaging revealed hyperintense signals in the splenium and genu of the corpus callosum and a white matter lesion of the left hemisphere in diffusion-weighted imaging. The initial, tentative diagnosis was clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). We initiated intravenous methylprednisolone pulse therapy; thereafter, her level of consciousness rapidly improved. On admission, thyroid function studies revealed elevation of free thyroxine and a low level of thyroid stimulating hormone with thyroid-related autoantibodies. She was begun on thiamazole and was discharged without neurological sequelae. CONCLUSION: Thyroid crisis is similar to acute encephalitis or encephalopathy associated with viral infection, especially with MERS, because the clinical and radiological features resemble those of thyroid crisis; therefore, thyroid diseases should be considered as a possible cause of reversible lesions in the splenium of the corpus callosum.

[Paradoxical effect of levetiracetam on seizure suppression: three cases showing U curve association between dose and effect].

We experienced 3 adult patients with intractable focal epilepsy treated by levetiracetam (LEV) as polytherapy, who showed paradoxical effect (PE). Starting dose of LEV was small (62.5, 250 mg/day) and we gradually increased by less than 250 mg/day, every more than 2 weeks. Within 6 months after LEV was added, LEV of 750 to 1,000 mg/day brought reduction of seizure frequency. Serum concentration of LEV was 13.3 and 14.0 µg/ml. In order to obtain better seizure control, LEV was increased up to 1,000-2,500 mg/day (19.3-35.0 µg/ml) within one year, and they developed PE. They all showed increased habitual seizures, occurring in cluster. Once dose of LEV deceased down to what produced the maximum seizure suppression, all of the patients regained the better seizure control. It is most likely that at least in some patients like present 3 cases, PE of LEV may express U curve association between dose and effect and that it was only delineated by slow titration.

Surgical resection for ruptured aneurysm of middle colic artery caused by segmental arterial mediolysis: a case report.

Aneurysm of the middle colic artery is very uncommon. In this report, we describe a case of a ruptured aneurysm of the middle colic artery caused by segmental arterial mediolysis and its successful management by surgical resection. A 60-year-old Japanese man was admitted to our institution for the treatment of a ruptured aneurysm of the branch of the superior mesenteric artery suspected by computed tomography. Angiography revealed multiple wide and narrow mural irregularities and some aneurysms in the middle colic artery without extravasation. Transcatheter arterial embolization could not be accomplished because of difficulty in catheterization. Since radiological findings of the patient indicated worsening of the aneurysm, surgical resection was performed. Histopathological findings of the resected specimen were consistent with those of segmental arterial mediolysis. In cases where curative embolization cannot be accomplished, surgical resection is required. However, in a non-ruptured aneurysm, healing occurs gradually. Therefore, if the vital parameters of the patient are stable, conservative observation can be recommended.

[Study of an efficacy and a pharmacokinetics of intranasal midazolam for status epilepticus on childhood epilepsy].

We reviewed the efficacy and a pharmacokinetics of intranasal midazolam (MDL) for status epilepticus in childhood epilepsies. This trial was planned for the patients who developed status epilepticus at least once in the past and had no responses with diazepam. Intranasal midazolam was proved to be effective (complete remission;65%), rapidly (an average time to stop seizures; 5.7 min) and safe with no adverse effects including respiratory depression with this dosage (an average of 0.26 mg/kg). In patients whose longitudinal concentrations of MDL in the blood were measured, MDL level was increased rapidly within five minutes after nasal application. Intranasal MDL is useful as a simple and safe method in the child emergency situation.

[Convulsive syncope then convulsive seizure occurred in the long clinical course: a case report].

A 17-year-old woman presented with transient consciousness impairment attack and convulsion after bathing and prolonged standing since age 12. EEG showed WHAM ( wake, high amplitude, anterior, male) type of phantom spikes that usually carry the high risk of epilepsy at age 13. At age 17, EEG wise generalized spike and wave complex was recorded once, and head-up tilt test was positive. She was carefully observed without antiepileptic drugs since convulsive syncope due to neurally mediated syncope was most likely. During the follow-up period, she had eventually unprovoked generalized tonic-clonic seizures (convulsive seizure) twice and thus she was started with antiepileptic drug with success. Although both convulsive syncope and convulsive seizure differ in nature and effects on quality of life, in this patient, the latter occurred later and both occurs together. It is important to distinguish them by means of the degree of convulsion and EEG finding.

Mid-term outcomes of valve-sparing root reimplantation with leaflet repair.

OBJECTIVES: Valve repair for aortic insufficiency (AI) requires a tailored surgical approach determined by the leaflet and aortic disease. In this study, we used a repair-oriented system for the classification of AI, and we elucidated long-term outcomes of aortic root reimplantation with this classification system. METHODS: From 1999 to 2018, a total of 197 patients underwent elective reimplantation (mean age: 52.7 ± 17.7 years; 80% male). The aortic valve was tricuspid in 143 patients, bicuspid in 51 patients and quadricuspid in 3 patients. A total of 93 patients had type I AI (aortic dilatation), 57 patients had type II AI (cusp prolapse) and 47 patients had type III AI (restrictive). In total, 104 of the 264 patients (39%) had more than 1 identified mechanism. RESULTS: In-hospital mortality was 0.5% (1/197). Mid-term follow-up (mean follow-up duration: 5.5 years) revealed a late mortality rate of 4.2% (9/197). Aortic valve reoperation was performed on 16 patients (8.0%). Rates of freedom from aortic valve replacement and freedom from aortic valve-related events at 10 years of follow-up were 87.0 ± 4.0% and 60.6 ± 6.0%, respectively; patients with type Ib AI (98.3 ± 1.7%; 80.7 ± 7.5%) had better outcomes than patients with type III AI (59.6 ± 15.6%; 42.2 ± 13.1%, P = 0.01). In patients with types II and III AI who had bicuspid aortic valves, rates of freedom from aortic valve-related events at 5 years of follow-up were 95.2 ± 4.7% and 71.7 ± 9.1%, respectively (P = 0.03). CONCLUSIONS: This repair-oriented system for classifying AI could help to predict the durable aortic valve repair techniques. Patient selection according to the classification is particularly important for long-term durability. CLINICAL TRIAL REGISTRATION NUMBER: B190050.

A successful report of mitral valve repair for parachute-like mitral valve in adult.

A 65 year-old man was diagnosed with congestive heart failure secondary to severe mitral regurgitation resulting from a parachute-like asymmetrical mitral valve. We performed mitral annuloplasty and triangular resection of the thick tissue. The postoperative course was uneventful with no recurrence of mitral regurgitation.

A unique case of collagenous colitis presenting as protein-losing enteropathy successfully treated with prednisolone.

A 76-year-old woman with a 5-mo history of recurrent diarrhea and generalized edema was admitted to our hospital. Colonoscopy revealed edematous mucosa, and histopathological examination was compatible with collagenous colitis. Protein leakage from the colon, particularly in the ascending portion, was identified on 99mTc-human serum albumin scintigraphy. Collagenous colitis associated with protein-losing enteropathy (PLE) without small bowel disease was diagnosed. Prednisolone treatment ameliorated diarrhea and hypoproteinemia. Collagenous colitis should be included in the differential diagnosis of chronic diarrhea with hypoproteinemia for appropriate management.

[Clinical relevance of antidepressant-induced activation syndrome: from a perspective of bipolar spectrum disorder].

Recent concerns have been raised regarding whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) might increase suicidal tendencies and intense debate-rages over the pros and cons of their use. Although systematic reviews and population-based studies have been conducted, a consensus on this association remains to be established. Subsequently, the concept of so-called 'activation syndrome' associated with antidepressants has been accepted without its adequate verification. In the present report, we present our experience of seven cases considered of having 'activation syndrome' brought on by antidepressants, and examine its clinical relevance to bipolar spectrum disorder (Ghaemi, et al., 2001) both symptomatologically and diagnostically. Five patients, diagnosed as having major depressive disorder according to the diagnostic manual (DSM-IV), met the criteria of bipolar spectrum disorder and suffered from activation syndrome following the administration of SSRIs, mainly paroxetine. Similarly, hypomania developed in all five cases with depression; the diagnostic criteria of a hypomanic episode were not met. In the remaining two patients, who were both diagnosed with bipolar disorder, one showed irritability and insomnia through imipramine use, and the another developed a hypomanic and/or a mixed state after the co-administration of fluvoxamine and trazodone. From the results of our examination, 'bipolarity', which is the pivotal factor of bipolar spectrum, might exist behind the phenomenon recognized as activation syndrome, and be revealed by antidepressant treatment, just like manic switching. Moreover, the various problems encountered in the current practice of treating mood disorders, including unipolar-bipolar dichotomy, manic switching by antidepressants, and narrow criteria for a mixed episode, were pointed out a new through this concept of activation syndrome. Actually, the understanding of activation syndrome clinically leads to the prevention of suicidal behavior and the careful use of antidepressants for bipolar (spectrum) disorder, but we must be prudent when applying this concept, since it has not yet been established.

Clinical outcomes of combined aortic root reimplantation technique and total arch replacement.

OBJECTIVES: The goal of this study was to evaluate early and late outcomes of combined valve-sparing aortic root replacement and total arch replacement (TAR). METHODS: From October 1999 to May 2014, 195 patients underwent valve-sparing operations using the David reimplantation technique. Thirty-one patients underwent combined TAR for aortic regurgitation (AR) with extended aortic aneurysm from the aortic root to the aortic arch. Aetiologies included acute type A aortic dissection in 12 cases, chronic aortic dissection in 8 cases and non-dissecting aneurysm in 11 cases. There were 9 patients with Marfan syndrome. The preoperative severity of AR was mild in 4, moderate in 16 and severe in 11. Even though half of those were emergent operations for acute aortic dissection, preoperative haemodynamic conditions were stable in all patients. RESULTS: No hospital deaths occurred. Postoperative complications included prolonged mechanical ventilation (>48 h) in 1 case and re-exploration for bleeding in 2 cases. Other complications, such as neurological dysfunction or low cardiac output syndrome, were not observed. At hospital discharge, 2 patients had mild AR, 22 had trace AR and 7 had no AR. During follow-up, 2 patients had moderate AR, 7 had mild AR, 18 had trace AR and 3 had no AR. Follow-up was completed in 95.1% of patients, and the mean follow-up period was 60.5 ± 9.1 months. No late death and thromboembolic complication occurred during follow-up. One patient required reoperation for AR. Freedom from reoperation at 5 and 10 years was 100 ± 0 and 83.3 ± 3.5%, respectively. Freedom from moderate or severe AR at 3 and 5 years was 83.3 ± 3.5 and 83.3 ± 3.5%, respectively. CONCLUSIONS: Early outcomes of combined aortic root reimplantation and TAR were satisfactory and provided excellent freedom from thromboembolic complication. The rate of freedom from reoperation during long-term follow-up was acceptable. Further follow-up is required to evaluate this procedure.

Mid-Term Results of Valve-Sparing Aortic Root Replacement in Patients With Expanded Indications.

BACKGROUND: The mid-term results of valve-sparing aortic root reimplantation (VSRR) for various indications were investigated. METHODS: From 2000 to 2013, 183 consecutive patients undergoing VSRR were enrolled. Expanded indications, defined as a patient on the marginal operative indication, included age 65 years or older (n = 33), age 15 years or younger (n = 4), acute type A aortic dissection (AAAD) (n = 21), aortitis (n = 8), reoperative root replacement (n = 11), cusp prolapse (n = 67), large aortoventricular junction of greater than 28 mm (AVJ) (n = 42), preoperative severe aortic regurgitation (AR) (n = 89), left ventricular ejection fraction 0.40 or less (n = 12), LV dilation (n = 66), New York Heart Association class III or greater (n = 5), need for total arch replacement (n = 29), and concomitant mitral valve repair (n = 12). RESULTS: The overall survival at 5 years was 96.6%. Freedom from greater than mild AR and reoperation at 5 years was 85.8% and 92.9%, respectively. Cox proportional hazard model revealed that AAAD, cusp prolapse, AVJ 28 mm or greater, and operation before 2009 were at risk for late AR recurrence (p = 0.015, p = 0.0041, p = 0.032, and p = 0.014, respectively). After 2009, freedom from late AR in the cusp prolapse group improved (p = 0.055, versus control). Both freedom from recurrent AR and reoperation were worse as the number of expanded indications increased (log-rank trend p = 0.00017 and p = 0.00067, respectively). CONCLUSIONS: Surgical outcomes of VSRR in these patient cohorts were satisfactory with some room for improvement in patients with cusp prolapse. Although the indications for VSRR are being expanded, a larger number of expanded indications were associated with poor outcomes in terms of longevity of valve function.

A prospective, open-label, flexible-dose study of quetiapine in the treatment of delirium.

BACKGROUND: Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impaired cognitive functioning. High-potency typical neuroleptics have traditionally been used as first-line drugs in the treatment of delirium. However, these drugs are frequently associated with undesirable adverse events including extrapyramidal symptoms (EPS). The purpose of the present open-label, flexible-dose study was to provide preliminary data on the usefulness and safety of quetiapine for patients with delirium. METHOD: Twelve patients with DSM-IV delirium were treated with flexible doses of open-label quetiapine (mean +/- SD dosage = 44.9 +/- 31.0 mg/day). To evaluate the usefulness and safety of quetiapine, scores from the Delirium Rating Scale, Japanese version, were assessed every day (for 1 outpatient, at least twice per week), and scores from the Mini-Mental State Examination, Japanese version, and the Drug-Induced Extrapyramidal Symptom Scale were assessed at baseline and after remission of delirium. Data were gathered from April to October 2001. RESULTS: All patients achieved remission of delirium several days after starting quetiapine (mean +/- SD duration until remission = 4.8 +/- 3.5 days). Quetiapine treatment was well tolerated, and no clinically relevant change in EPS was detected. CONCLUSION: Quetiapine may be a useful alternative to conventional neuroleptics in the treatment of delirium due to its rapid onset and relative lack of adverse events. Further double-blind, placebo-controlled studies are warranted.