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.

[The Efficacy of a Released Ultrasonic Lithotripsy in Percutaneous Nephrolithotomy : Randomized Trial Comparing Swiss LithoClast® Master Versus Swiss LithoClast®].

We prospectively randomized total 29 patients with renal stones into two groups between Aug 2014 and March 2016. The US group was treated using a ultrasonic lithotripter (Swiss LithoClast® Master) and the PN group was treated with a pneumatic lithotripter (Swiss LithoClast® ). We compared treatment outcomes in these groups. The US group consisted of 17 patients and the PN group 12 patients. There was no significant difference between the groups in baseline characteristics (age, sex, body mass index, side, stone size, and density). There was no significant difference in total operative time (p＝0.63), stone-free rate (p＝ 0.19), hemoglobin deficit (p＝0.49), or rate of postoperative sepsis (p＝0.99) between the two groups. However, intracorporal stone disintegration and removal time was significantly shorter in the US group than the PN group (p＝0.029). These results suggest that the ultrasonic lithotripter can be superior to the existing pneumatic lithotripter in saving intracorporal stone disintegration and removal time in percutaneous nephrolithotomy.

[A Case of Adrenergic Crisis Caused by Spontaneous Rupture of Cystic Pheochromocytoma].

Pheochromocytoma crisis is a life-threatening situation. Herein we report a case of catecholamineinduced crisis caused by the rupture of cystic pheochromocytoma. A 76-year-old man with hypertension was referred to our hospital because of a cystic tumor in the retroperitoneal space adjacent to the aorta, which was suspicious of pheochromocytoma. Two days after admission, lower abdominal pain suddenly appeared, followed by hypertension with systolic pressure of 260 mmHg. Computed tomography revealed that the cystic tumor was ruptured spontaneously, leading to diagnosis of pheochromocytoma crisis. His blood pressure was successfully managed by medical treatment and he could recover from crisis. After adequate medical preparation by an α-adrenergic blocker, the tumor was successfully removed by laparoscopy, though the adhesion around the tumor was severe. To our knowledge adrenergic crisis caused by spontaneous rupture of cystic pheochromocytoma is rare, but we have to keep in mind that cystic pheochromocytoma can cause life-threatening crisis by the release of catecholamine due to rupture.

[TREATMENT OUTCOME OF OBSTRUCTIVE PYELONEPHRITIS DUE TO URETERAL CALCULI WITH DISSEMINATED INTRAVASCULAR COAGULOPATHY].

OBJECTIVES: Because obstructive pyelonephritis secondary to ureteral stones can easily cause sepsis and concomitant disseminated intravascular coagulation (DIC), it is a potentially lethal disease. However, the optimal treatment for such severe patients has yet to be established. In this study, we aimed at clarifying the effectiveness of emergent drainage and DIC treatments for patients with septic DIC due to obstructive pyelonephritis. In additon, we also evaluated the impact of recombinant human thrombomodullin (rTM) for severe patients with DIC. MATERIALS AND METHODS: From September 2006 to May 2013, 31 patients with obstructive pyelonephritis secondary to ureteral stones who met the acute DIC criteria from the Japanese Association of Acute Medicine were treated at our institution. All patients received emergent drainage of urinary tract and anti-DIC treatment, as well as administration of antibiotics and adequate volume infusion. To evaluate the impact of rTM, patients received rTM were compared with those managed by other DIC therapeutic agents. RESULTS: The mean patients' age was 73 years old, and 27 patients (87.1%) were in a state of septic shock. All patients, except for one patient (3.2%) who died 6 days after drainage, could recover from sepsis and comcomitant DIC. Interestingly, thrombocyte count, creatinine, and SOFA Score in rTM group were recovered faster than those in no rTM group (p = 0.017, 0.0038, and 0.0006, respectively). CONCLUSIONS: These results indicate that most patients with DIC caused by obstractive pyelonephritis can be successfully managed by emergency drainage and anti-DIC treatment. In addition, rTM may be effective for the treatment of such severe patients by improving organ failure associated with disordered coagulation.

[Treatment outcome of laparoscopic radical cystectomy at a single institution].

OBJECTIVE: The standard care for invasive bladder cancer is radical cystectomy with urinary diversion, but laparoscopic radical cystectomy (LRC) is still being evaluated. We describe our initial experience of laparoscopic radical cystectomy compared to open radical cystectomy (ORC). PATIENTS AND METHODS: From January 2000 to June 2012, 84 patients underwent radical cystectomy by ORC (n = 54) or LRC (n = 30). Treatment outcomes including surgical and oncological outcomes between LRC and ORC were compared. We also assessed learning curve during LRC as to blood loss, operating time and complication rate. RESULTS: The patients' characteristics were similar in LRC and ORC groups except for ASA score. Importantly, Operating time during LRC was longer but complication rate of LRC was lower than that of ORC (586 min vs 424 min and 40% vs 69%, respectively). In addition, pathological stage or outcomes were similar in both groups and there were no significant difference between LRC and ORC groups in terms of overall and recurrence free survival rate. As for learning curve of LRC, operating time and blood loss tended to decrease with increased experience. CONCLUSION: These results indicate that LRC could be performed safely with decreased complication rate and similar oncological outcomes compared to ORC.

Intravenous Thrombolysis With Alteplase at 0.6 mg/kg in Patients With Ischemic Stroke Taking Direct Oral Anticoagulants.

Background We elucidated the safety of treatment with alteplase at 0.6 mg/kg within 24 hours for patients on direct oral anticoagulants (DOACs) before ischemic stroke onset. Methods and Results Consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis using alteplase at 0.6 mg/kg from 2011 to 2021 were enrolled from our single-center prospective stroke registry. We compared outcomes between patients taking DOACs and those not taking oral anticoagulants within 48 hours of stroke onset. The primary safety outcome was the rate of symptomatic intracranial hemorrhage with a ≥4-point increase on the National Institutes of Health Stroke Scale score from baseline. The efficacy outcome was defined as 3-month modified Rankin Scale score of 0 to 2 after stroke onset. Of 915 patients with acute ischemic stroke who received intravenous thrombolysis (358 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 10), 40 patients took DOACs (6 took dabigatran, 8 took rivaroxaban, 16 took apixaban, and 10 took edoxaban) within 24 hours of onset and 753 patients did not take any oral anticoagulants. The rate of symptomatic intracranial hemorrhage was comparable between patients on DOACs and those not on oral anticoagulants (2.5% versus 2.4%, P=0.95). The rate of favorable outcomes was comparable between the 2 groups (59.4% versus 58.2%, P=0.46), although the admission National Institutes of Health Stroke Scale score was higher in patients on DOACs. No significant differences showed in any intracranial hemorrhage within 36 hours or mortality at 3 months. Conclusions Intravenous thrombolysis would be safely performed for patients on DOACs following the recommendations of the Japanese guidelines. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02251665.

Trajectories of Healthcare Utilization Among Children and Adolescents With Autism Spectrum Disorder and/or Attention-Deficit/Hyperactivity Disorder in Japan.

BACKGROUND: Early intervention and prevention of psychiatric comorbidities of children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are urgent issues. However, the differences in the diagnoses of ASD and ADHD and psychiatric comorbidities associated with age, long-term healthcare utilization trajectories, and its associated diagnostic features have not been fully elucidated in Japan. METHOD: We conducted a retrospective observational study using the medical records. Member hospitals of three major consortiums of hospitals providing child and adolescent psychiatric services in Japan were recruited for the study. Children who accessed the psychiatry services of the participating hospitals in April 2015 were followed up for 5 years, and data on their clinical diagnoses, consultation numbers, and hospitalizations were collected. Non-hierarchical clustering was performed using two 10-timepoint longitudinal variables: consultation numbers and hospitalization. Among the major clusters, the differences in the prevalence of ASD, ADHD, comorbid intellectual disability, neurotic disorders, and other psychiatric disorders were assessed. RESULTS: A total of 44 facilities participated in the study (59.5%), and 1,003 participants were enrolled. Among them, 591 diagnosed with ASD and/or ADHD (58.9%) and 589 without missing data were assessed. The mean age was 10.1 years, and 363 (70.9%) were boys. Compared with the pre-schoolers, the school-aged children and adolescents had fewer ASD, more ADHD, and fewer comorbid intellectual disability diagnoses, as well as more diagnoses of other psychiatric disorders. A total of 309 participants (54.7%) continued consultation for 2 years, and 207 (35.1%) continued for 5 years. Clustering analysis identified three, two, and three major clusters among pre-schoolers, school-aged children, and adolescents, respectively. The largest cluster was characterized by early termination of the consultation and accounted for 55.4, 70.6, and 73.4% of pre-schoolers, school-aged children, and adolescents, respectively. Among the school-aged children, the diagnosis of ADHD was associated with a cluster that required longer periods of consultations. Among the adolescents, comorbid psychiatric disorders other than intellectual disability and neurotic disorders were associated with clusters that required hospitalization. CONCLUSION: Continuous healthcare needs were common and psychiatric comorbidities were associated with complex trajectory among adolescents. The promotion of early intervention and prevention of comorbidities are important.

Elevated serum lipase levels in patients with dyspepsia of unknown cause in general practice.

OBJECTIVE: To study the cause(s) of chronic dyspepsia among patients with no findings on general practice screening tests. MATERIALS AND METHODS: A total of 272 consecutive patients at a general practice in Japan (125 males and 147 females, aged 14-89 years) who underwent abdominal ultrasound (US) and who had serum pancreatic enzyme (lipase or p-amylase) levels measured, were included in a 1-year study. Serum pancreatic enzyme levels were compared according to the duration of the symptoms and causes of dyspepsia, and then compared between two groups: a 'known-cause group' of 38 patients in whom the cause of the chronic (over 1 month) dyspepsia was determined by US or other diagnostic procedures; and an 'unknown-cause group' of 112 patients in whom no cause was found. RESULTS: The mean lipase level in the unknown-cause group was significantly higher than that in the known-cause group (40.6 vs. 35.3 U/l, p = 0.008 after adjustment for age, sex, and serum creatinine). No difference between these groups was found for p-amylase. The proportion of patients with high lipase levels (above reference range) was higher in the unknown-cause group compared to the known-cause group, although this was not significant (21.4 vs. 10.5%). CONCLUSION: Our data showed that serum lipase levels were higher in patients with chronic dyspepsia of unknown than in those with a known cause. We therefore speculate that mild functional pancreatic disorder may underlie some cases with unexplainable chronic dyspepsia.

Clot regression effects of rivaroxaban in the treatment of venous thromboembolism in patients with cancer (CRERIT-VTE cancer): study protocol.

INTRODUCTION: Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE. METHODS AND ANALYSIS: This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.Trial registration numberUMIN000027793.

Successful Post-Transplant Psychiatric Interventions During Long-Term Follow-Up of Patients Receiving Liver Transplants for Alcoholic Liver Disease.

BACKGROUND Around 20-30% of patients who undergo liver transplantation (LT) for alcoholic liver disease (ALD) will resume heavy drinking after LT. It is crucial to control post-transplant relapse of alcohol use, because alcoholic recidivism has been shown to have a negative impact on post-transplant compliance and long-term outcomes of LT recipients. However, there is currently no specific, effective psychiatric intervention for preventing additional alcohol consumption in clinical practice. CASE REPORT We present 3 patients who underwent LT for ALD at Nagoya University Hospital who were followed up for prolonged periods (7.2, 8.8, and 11.3 years, respectively), and review the psychiatric interventions employed to address critical situations. Additional alcohol consumption was noted in Case 1, but prompt collaborative care led to stable abstinence. In Case 2, marked anger and irritation were exacerbated as a result of work, but the anger was controlled by anger management. Case 3 abused a minor tranquilizer, but limit-setting resulted in adequate medical adherence. CONCLUSIONS Transplant teams need to provide comprehensive treatment for alcoholic recidivism to improve long-term health after LT for ALD.