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A cardiac herniation is a rare but life-threatening complication after pneumonectomy. In most cases, it manifests suddenly as severe hypotension and cardiac arrest within 24 h of pneumonectomy. Here, we report a case of sudden-onset cardiac herniation after right pneumonectomy during which the pericardium was incised. The diagnosis was made immediately based on chest X-ray and electrocardiogram findings, and the heart was repositioned by repeat thoracotomy as an urgent life-saving measure. Surgeons should be aware of this potential surgical complication as well as its clinical manifestations, given that delayed diagnosis would directly lead to a fatal outcome.

Background Rectal gastrointestinal stromal tumours (GISTs) are rare and treated mainly by radical surgery. Although the importance of perioperative imatinib has been recognized, there are few reports on its outcomes. Method Consecutive patients diagnosed with rectal GISTs between July 2008 and February 2021 were identified from a prospective database. Effects of perioperative imatinib were investigated, and surgical and survival outcomes were compared between neoadjuvant imatinib and upfront surgery. Results 34 patients meeting the inclusion criteria were identified. Compared with upfront surgery (n = 11), the neoadjuvant imatinib group (n = 23) had significantly larger tumours (median size 8.3 versus 2.5 cm; P = 0.01) and included a significantly greater proportion of high-risk patients according to the modified Fletcher classification (20/23 (87.0%) versus 6/11 (54.5%); P = 0.02). Comparing the operation planned based on imaging before neoadjuvant imatinib and the operation performed, there was an increase in sphincter-preserving surgery (4/23 (17.4%) to 11/23 (47.8%); P = 0.02), abdominoperineal resection 11/23 (47.8%) reduced to 7/23 (30.4%); P = 0.13) and total pelvic exenteration reduced from 8/23 (34.8%) to 5/23 (21.7%); P = 0.01). Tumours were downsized by a median of 30 per cent (range 0 per cent to −56 per cent; P = 0.01). During follow-up (median 42, range 5–131 months), there was no postoperative recurrence in 29 patients who received perioperative imatinib. One of the five patients who underwent surgery without neoadjuvant or adjuvant imatinib developed local recurrence. Conclusion Treatment with imatinib for rectal GISTs seems to improve outcomes, and neoadjuvant imatinib increases the rate of sphincter-preserving surgery.

Imaging diagnosis is essential to perform appropriate reperfusion therapy for acute ischemic stroke. To equally perform reperfusion therapy all over in Japan, it is important to properly facilitate acute imaging evaluation for stroke suspected patients by medical staff not only in stroke-specialized hospitals but also in non-stroke-specialized hospitals. It is unique that CT and MRI are available in most of Japanese hospitals. Even in non-stroke-specialized hospitals, inpatients may suffer from in-hospital stroke. We review statements and recommendation items for a diagnostic imaging to appropriately perform reperfusion therapy based on major clinical trials, stroke guidelines and the current status of acute stroke imaging in Japan.

BackgroundWe aimed to identify the large ischemic core (LIC) volume ranges in acute ischemic stroke patients that can benefit from mechanical thrombectomy (MT).MethodsConsecutive patients within 24 hours of onset of anterior circulation ischemic stroke with large vessel occlusion and ischemic core volumes of 70–300 mL were included from our single-center prospective database from March 2014 to December 2019. Subjects were divided into three groups by baseline ischemic core volume (A: 70–100 mL; B: 101–130 mL; C: >130 mL). We compared modified Rankin Scale (mRS) score 0–2 at 3 months and parenchymal hematoma between patients receiving MT and standard medical treatment (SMT), and determined clinically treatable core volume ranges for MT.ResultsOf 157 patients (86 women; median age, 81 years; median ischemic core volume, 123 mL), 49 patients underwent MT. In Group A (n=52), MT patients (n=31) showed a higher proportion of mRS 0–2 at 3 months (52% vs 5%, PConclusionsIschemic core volumes between 70 and 100 mL may benefit from MT. The treatable upper core limit is approximately 120 mL in selected patients with LIC of 70–300 mL.

Background Tenecteplase has higher fibrin specificity with a longer half-life and the potential to achieve higher rates of recanalization than alteplase. A critical limitation of tenecteplase is no commercial use in Japan and no experience with its administration to Japanese patients. Hypothesis Tenecteplase is superior to alteplase in achieving recanalization on the initial angiogram when administered ≤4.5-hour of stroke onset in patients planned for mechanical thrombectomy (MT) in Japan where alteplase at the unique dose of 0.6mg/kg is officially used. Methods The Tenecteplase versus alteplase For LArge Vessel Occlusion Recanalization (T-FLAVOR) trial is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, masked-endpoint, superiority study. Eligibility criteria include acute ischemic stroke with pre-stroke modified Rankin Scale score ≤3 and large vessel occlusion (internal carotid artery, middle cerebral artery, or basilar artery) eligible for intravenous thrombolysis ≤4.5-hour and MT ≤6-hour of stroke onset. After completing the safety confirmation phase involving three patients who received non-masked tenecteplase (0.25 mg/kg), 220 patients will be randomized to two groups (1:1), intravenous alteplase (0.6mg/kg, n = 110) or tenecteplase (0.25mg/kg, n = 110), prior to MT. Outcomes In the safety confirmation phase, the primary outcome is symptomatic intracranial hemorrhage (sICH) ≤24-36-hour. In the randomized, comparative phase, the primary efficacy outcome is substantial angiographic reperfusion (mTICI grade 2b/2c/3) or absence of retrievable thrombus on the initial angiogram. The primary safety outcome is sICH ≤24-36-hour and 90-day mortality. Discussion T-FLAVOR may help determine if tenecteplase should be recommended as a routine clinical strategy before MT for Japanese stroke patients. Trial registration jRCTs051210055

Background: Adrenomedullin (AM), an endogenous peptide, is secreted in response to cerebral ischemia, contributing to neuroprotection by exerting anti-inflammatory and vasodilatory effects. Although previous studies showed elevated levels of mid-regional fragment of pro-AM (MR-proAM), a stable marker of AM, predict unfavorable outcome in acute ischemic stroke (AIS), the role of the biomarker remains to be determined. Methods: Firstly, plasma MR-proAM levels were measured in consecutively enrolled patients with AIS within 4.5 hours of the onset and compared with those of healthy controls. Propensity score was used to match the baseline difference. Secondly, variables associated with the increased MR-proAM levels were evaluated in AIS. Finally, it was determined whether MR-proAM levels are associated with a large penumbra which was defined as ICA/M1 occlusion with NIH stroke scale ≥ 6 and ischemic core volume ≤ 50 ml calculated by the RAPID software. Results: MR-proAM levels in AIS (n = 122; median age, 77 years; male, 59%; median NIHSS 6.5) were higher (median 0.68 vs. 0.42 nmol/L, p < 0.001) compared with controls (n = 1298; median age, 58 years; male, 33%). The difference remained after matching of baseline (p=0.004). In patients with AIS, MR-proAM levels were correlated with NIHSS (r = 0.367, p < 0.001) and eGFR (r = -0.527, p < 0.001). MR-proAM levels did not correlate with ischemic core volume (r = 0.065, p = 0.478), but significantly increased in AIS patients with cardioembolic stroke (CES) (n = 53) (0.80 vs. 0.59 nmol/L, p < 0.001) and ICA/M1 occlusion (n = 40) (0.78 vs. 0.63 nmol/L, p = 0.048). Interestingly, MR-proAM levels were higher (0.85 vs. 0.62, p < 0.001) in AIS patients with a large penumbra (n = 24) compared to those without (n = 98), and the difference remained after adjustment of baseline factors (OR [95% confidence interval], 1.43 [1.10-2.02], p = 0.004). Conclusions: MR-proAM levels increase in patients with AIS, especially in those with large vessel occlusion and clinical imaging mismatch. MR-proAM is a potential biomarker for ischemic penumbra.

OBJECTIVES The management of acute type A aortic dissection with malperfusion syndrome remains challenging. To evaluate preoperative condition, symptoms might be subjective and objective evaluation of cerebral artery has not yet been established. For quantitative evaluation, this study focused on brain computed tomography perfusion (CTP), which has been recommended by several guidelines of acute ischaemic stroke. METHODS In the last 2 years, 147 patients hospitalized due to acute type A aortic dissection were retrospectively reviewed. Among the 23 (16%) patients with cerebral malperfusion, 14 who underwent brain CTP (6 preoperative and 8 postoperative) were enrolled. CTP parameters, including regional blood flow and time to maximum, were automatically computed using RApid processing of Perfusion and Diffusion software. The median duration from the onset to hospital arrival was 129 (31–659) min. RESULTS Among the 6 patients who underwent preoperative CTP, 4 with salvageable ischaemic lesion (penumbra: 8–735 ml) without massive irreversible ischaemic lesion (ischaemic core: 0–31 ml) achieved acceptable neurological outcomes after emergency aortic replacement regardless of preoperative neurological severity. In contrast, 2 patients with an ischaemic core of >50 ml (73, 51 ml) fell into a vegetative state or neurological death due to intracranial haemorrhage. CTP parameters guided postoperative blood pressure augmentation without additional supra-aortic vessel intervention in the 8 patients who underwent postoperative CTP, among whom 6 achieved normal neurological function regardless of common carotid true lumen stenosis severity. CONCLUSIONS CTP was able to detect irreversible ischaemic core, guide critical decisions in preoperative patients and aid in determining the blood pressure augmentation for postoperative management focusing on residual brain ischaemia.

The 2 km long suspension bridge with a main span greater than 1 km which crosses the Danube River is the focal point of the 23 km highway project in Braila/ Romania. The bridge will carry two lanes of highway traffic in each direction. IHI Infrastructure Systems Co., Ltd. is the EPC contractor for the project together with Astaldi SpA.To accelerate the bridge construction, the slip-form method was chosen for the construction of the concrete pylons and precast cross beams were installed by the heavy lifting method. This paper discusses the effects of the pylon’s construction method on the structural design and geometry control of the pylons during construction.

Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., ‘right-sided colon vs. left-sided colon,’ ‘colon vs. rectum,’ and ‘right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).’ This nationwide multicenter retrospective study aimed to clarify the prognostic impact of tumor location in patients with stage III colorectal cancer by classifying tumors into three groups: right-sided colon, left-sided colon, and rectum. Subjects were 9194 patients with stage III colorectal cancer who underwent curative surgery from 1997 to 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined. Rectal cancer (n = 2922) was associated with worse RFS compared to right-sided colon cancer (n = 2362) (hazard ratio (HR) 0.65; 95% CI 0.59–0.72; p

The feasibility of laparoscopic surgery for elderly patients remains unclear, as these patients usually present with comorbidities. Recently, the controlling nutritional status (CONUT) score has drawn attention as an evaluation score of patients' general status as well as a predictor of survival. We retrospectively analyzed overall survival in 424 patients aged ≥75 years with colon cancer, who underwent curative surgery (laparoscopic (

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.

During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9–2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02–3.00). Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Endovascular therapy is strongly recommended for acute cerebral large vessel occlusion (LVO) with an Alberta stroke program early computed tomography score (ASPECTS) ≥6 due to occlusion of the internal carotid artery or M1 segment of the middle cerebral artery. However, the effect of endovascular therapy for patients with a large ischemic core with an ASPECTS ≤5 (0-5) was not established. A multicenter, randomized, open-label, parallel-group trial was conducted to investigate the superiority of endovascular therapy over medical therapy without endovascular therapy for a large ischemic core with ASPECTS (3-5). Patients were randomly assigned to receive endovascular therapy or without endovascular therapy at a ratio of 1:1. The primary outcome was a moderate functional outcome, defined as a modified Rankin scale (mRS; scores ranging from 0 [no symptoms] to 6 [death]) ≤3 after 90 days. The secondary outcomes were defined as ordinal mRS, good functional outcome (mRS ≤2), excellent functional outcome (mRS ≤1), mRS shift analysis after 90 days, and early improvement of neurological findings at 48 hours. A total sample size of 200 was estimated to provide a power of 0.9 with a two-sided alpha of 0.05, for the primary outcome, considering a 15% dropout rate. This randomized clinical trial reported the applicability of endovascular therapy in patients with acute cerebral LVO with a large ischemic core.

A 79-year-old woman presented 3 years' history of hand shaking while drinking a cup of tea. The tremor was seen bilaterally, more predominantly on the left, and it also appeared when reading a book or writing. It was also induced by flexing the elbow to about 90 degrees or more without any specific task. Although there was no family history, the tremor in the present case was clinically diagnosed as essential tremor, because there were no other movement abnormalities, and other causes of tremor were excluded by laboratory tests. The tremor was dependent on the position of the involved extremity regardless of the kind of tasks. Position-specific tremor is discussed in relation to postural tremor.

Highlights • Intravenous immunoglobulin treatment improved muscle weakness and blurred vision. • Visual evoked potential showed a post-treatment shortening of P100 latency. • Treatment effects were consistently observed for 3.5 years., Background Multifocal motor neuropathy (MMN) occasionally presents with cranial nerve involvement. However, no MMN cases with visual pathway impairment demonstrated by visual evoked potential (VEP) have been reported. Case report A 36-year-old man was admitted to our hospital with progressive muscular weakness. On admission, neurological findings revealed bilateral muscle weakness and atrophy of the distal upper limbs. The blood tests were positive for GM-1 ganglioside antibodies. Nerve conduction studies revealed bilateral conduction block in the median nerve. He was diagnosed with MMN. Intravenous immunoglobulin treatment improved muscle weakness and blurred vision, which was not a complaint when he was first seen. Moreover, VEP showed a post-treatment shortening of P100 latency. These treatment effects were consistently observed for 3.5 years. Significance Our findings suggested that MMN could affect the visual pathway through autoimmune mechanisms.

Background and aim We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke. Methods The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22–36 h, and 7–14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days. Results Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17–1.44), mixed distribution (RR 19.2, 95% CI: 3.94–93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78–349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( p = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3–4] vs. 0 [0–3]), compared with those with Conclusion New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.

We report herein the case of a 79-year-old woman who experienced difficulties in swallowing, dysarthria, dropped head, and muscle weakness associated with diurnal and day-to-day variation. We made a diagnosis of generalized myasthenia gravis (MG) with anti-acetylcholine receptor antibodies. Contrast-enhanced computed tomography showed no sign of thymoma. As the MG worsened, the patient presented with severe bradycardia. Chest compressions were performed on days 6 and 7 after admission and she underwent implantation of a temporary pacemaker. The arrhythmia resolved after strong immunosuppressive treatment, and anti-striational antibodies, including anti-muscular voltage-gated potassium channel-complex (Kv1.4) antibody and anti-titin antibody, were subsequently detected. This case implies the possible involvement of anti-striational antibodies in bradycardia.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

There is no clear evidence on the number of cases required to master the techniques required in robot-assisted surgery for different surgical fields and techniques. The purpose of this study was to clarify the learning curve of robot-assisted rectal surgery for malignant disease by surgical process.The study retrospectively analyzed robot-assisted rectal surgeries performed between April 2014 and July 2020 for which the operating time per process was measurable. The following learning curves were created using the cumulative sum (CUSUM) method: (1) console time required for total mesorectal excision (CUSUM tTME), (2) time from peritoneal incision to inferior mesenteric artery dissection (CUSUM tIMA), (3) time required to mobilize the descending and sigmoid colon (CUSUM tCM), and (4) time required to mobilize the rectum (CUSUM tRM). Each learning curve was classified into phases 1-3 and evaluated. A fifth learning curve was evaluated for robot-assisted lateral lymph node dissection (CUSUM tLLND).This study included 149 cases. Phase 1 consisted of 32 cases for CUSUM tTME, 30 for CUSUM tIMA, 21 for CUSUM tCM, and 30 for CUSUM tRM; the respective numbers were 54, 48, 45, and 61 in phase 2 and 63, 71, 83, and 58 in phase 3. There was no significant difference in the number of cases in each phase. Lateral lymph node dissection was initiated in the 76th case where robot-assisted rectal surgery was performed. For CUSUM tLLND, there were 12 cases in phase 1, 6 in phase 2, and 7 cases in phase 3.These findings suggest that the learning curve for robot-assisted rectal surgery is the same for all surgical processes. Surgeons who already have adequate experience in robot-assisted surgery may be able to acquire stable technique in a smaller number of cases when they start to learn other techniques.

Computerized tomography (CT) or magnetic resonance imaging (MRI) is indispensable for diagnosing acute ischemic stroke (AIS) patients who are candidates for recombinant tissue plasminogen activator (rt-PA) therapies, but further investigation concerning appropriate selection of therapy following advanced imaging including perfusion imaging has not yet been done. The 2018 AHA guidelines have recommended not to perform excessive time-consuming imaging before rt-PA. Here we describe two cases in which reperfusion therapy was decided based on advanced imaging. The first case was a 70-year-old woman with complaints of total aphasia and right unilateral spatial neglect. Her MRI revealed no apparent high signal area in diffusion-weighted image (DWI), and her magnetic resonance angiography (MRA) showed no large vessel occlusion. Subsequent perfusion-weighted image (PWI) analysis showed a unilateral perfusion deficit in the left middle cerebral artery (MCA) region. The other case was an 88-year-old man with complaints of minor unilateral spatial neglect, right conjugate deviation of the eyes, and dysarthria. His MRI also revealed no apparent high signal area in DWI, and MRA showed slight stenosis in the right middle MCA. Subsequent PWI analysis showed a unilateral perfusion deficit in the right MCA region. In both cases, intravenous rt-PA therapy was administered after the diagnosis of AIS and the patients responded well to the reperfusion therapy. When DWI is performed too early, detecting the ischemic core and differentiating between a diagnosis of stroke and stroke mimics is sometimes difficult. Evaluation of perfusion abnormalities in acute cases can be performed quickly, as shown in these cases. Although rt-PA can be given just by non-contrast CT with no hemorrhage, advanced imaging may be an option to identify difficult-to-diagnose patients who require reperfusion therapy.

OBJECTIVE We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. METHODS We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (

Background and Purpose: IV alteplase at 0.6 mg/kg for acute wake-up and unclear onset strokes was recommended in Japanese stroke guidelines in March 2019. We determined the safety and effectiveness of this newly recommended thrombolysis in clinical practice. Methods: This is a multicenter observational study, enrolling acute ischemic stroke patients with a time last-known-well >4.5 h who have a mismatch between DWI and FLAIR treated with intravenous alteplase. The safety outcomes are intracranial hemorrhage (ICH) with neurological deterioration within 36 h after thrombolysis, all cause deaths within 90 days, and adverse events. The efficacy outcomes are functionally independence defined as a mRS score of 0-1 at 90 days, and NIHSS change at 24h from baseline. Results: Between 2019 March and 2020 March, 63 patients (33 females; age, 74±11y; premorbid functionally independence, 50 (82%); median NIHSS on admission, 11) were enrolled at 14 hospitals. Of them, 40 patients (63%) recognized stroke symptoms at wake-up time, and median time between last-known-well and admission was 6.5 h. Baseline MRA showed any vessel occlusion in 52 patients (88%). IV alteplase was disrupted in one patient. Two patients (3%) had symptomatic ICH (≥4 increase in NIHSS) within 36 h. NIHSS change was -5.1±8.1. Twenty-one patients (36%) had functionally independence at discharge and there was no death during acute hospitalization. Of the overall 63 patients, 22 also underwent mechanical thrombectomy (36%, 72±9y, median NIHSS 16), showing no symptomatic ICH, mean NIHSS change of -8.9±7.5, and 8 patients (42%) had functionally independence at discharge. Conclusions: In clinical practice, IV alteplase for wake-up and unclear onset stroke patients with DWI-FLAIR mismatch seemed to be safe and effective compared with previous randomized control trials. Mechanical thrombectomy could be combined with alteplase safely and effectively.

Background and purpose: To assess the potential effect of prior antithrombotic medication for thrombolysis using alteplase at 0.6mg/kg in unknown onset stroke. Methods: This was a prespecified sub-analysis of a THAWS trial (an investigator-initiated, multicenter, randomized, open, blinded-endpoint trial). Stroke patients with a time last-known-well >4.5 h who had a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6mg/kg or standard medical treatment (SMT). Patients were dichotomized by taking prior antithrombotic medication. The favorable outcome defined as a modified Rankin Scale score of 0-1 at 90 days and any intracranial hemorrhage within 22-36 h were compared in each group. Results: Of 126 patients (intention-to-treat population), 68 received alteplase and 58 had SMT. Seventeen in the alteplase group and 23 in the SMT group took antithrombotic medication (10 with antiplatelet alone, 5 with anticoagulant alone and 2 with both in the IVT group, and 14, 8 and 1, respectively, in the SMT group) before stroke onset. Antithrombotic therapy was more frequently initiated within 24 hours after randomization in the SMT group than in the alteplase group (86% vs. 12%, p Conclusions: Alteplase at 0.6mg/kg appears more beneficial in patients with prior antithrombotic medication.

Background and Purpose: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. Methods: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded–end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Results: The median DWI-Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI ( P =0.026) and core volume ( P =0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33–30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87–43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients. Conclusions: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr ; Unique Identifier: UMIN000011630.

Background and PurposeThe novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.MethodsThis is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.ConclusionThe proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

BackgroundThe emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.MethodsThis study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.ResultsDuring the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p&nbsp

A 71-year-old man presented with progressive muscle weakness of the four limbs in November 2014. His symptoms had started from the left leg in 2008, resulting in frequent falls. In 2011, he became unable to stand up without a handrail due to weakness of the both legs. Physical examination showed almost symmetric muscle weakness of the arms and legs; MMT4. The CK level was slightly elevated of 304 IU/l. The patient was diagnosed as having inclusion body myositis based on the muscle biopsy findings showing many fibers with rimmed vacuoles in addition to mononuclear cell infiltrating into the endomysium, surrounding and sometimes invading into non-necrotic muscle fibers. Anti-PM/Scl-75 antibodies were positive. Muscle strength improved after intravenous immunoglobulin therapy, although the effect was only temporary. This rare case suggests the autoimmunological etiology in inclusion body myositis.

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Background: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure (SBP) levels achieved with intravenous nicardipine immediately after onset of intracerebral haemorrhage (ICH) on clinical outcomes were determined. Methods: A systematic review and individual patient data analysis of articles before October 1, 2020 identified on PubMed were performed. Prospective studies involving hyperacute ICH adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale (mRS) were eligible. Outcomes included death or disability at 90 days, defined as an mRS score of 4-6, and haematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography. Findings: Three studies met the eligibility criteria. Of 1,271 patients overall, 1,265 (age 62.6±13.0 years, 484 women) with available SBP data were included. Death or disability occurred in 38.2%, and haematoma expansion occurred in 17.4%. Mean hourly SBP during the initial 24 h was positively associated with death or disability [adjusted odds ratio (aOR) 1.12, 95% CI 1.00–1.26 per 10 mmHg] and haematoma expansion (1.16, 1.02–1.32). The association of SBP with death or disability was modified by race, baseline diastolic BP, and study population (higher SBP increased the risk in Asians, aOR 1.26, 95% CI 1.10–1.43). Mean hourly SBP from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Slower lowering of SBP to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00–1.05, per hour). Interpretation: Rapid lowering of SBP by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute ICH decreased early haematoma expansion and 90-day death or disability without increasing serious adverse events. Funding: Japan Agency for Medical Research and Development. Conflict of Interest: All of the following conflicts are outside the submitted work.Toyoda reports personal fees from Daiichi-Sankyo, Bayer Yakuhin, Bristol-Myers-Squibb (BMS), and Nippon Boehringer-Ingelheim (NBI). Ihara reports grants from Panasonic, Shimadzu Corporation, BMS, Otsuka Pharmaceutical, and personal fees from Daiichi-Sankyo, Eisai, and Bayer Yakuhin.Itabashi reports grants from Tohoku Fukushi University and NBI. Yamagami reports research grants from BMS; lecturer’s fees from Stryker, Terumo, Medtronic, Medico’s Hirata, Johnson and Johnson, Bayer, Daiichi-Sankyo, BMS, NBI, Takeda, and Otsuka Pharmaceutical; and membership of the advisory boards for Daiichi-Sankyo. Itabashi reports honoraria from Bayer, Eisai, BMS, Daiichi Sankyo, NBI, Takeda, Otsuka Pharmaceutical, Tanabe-Mitsubishi Parma, Pfizer, GE Healthcare Japan, Stryker, Medtronic, and Johnson and Johnson, and research support from Tohoku Fukushi University and NBI. Sakai reports grants from Daiichi-Sankyo, Jimro, Medtronic, Terumo, and honoraria from Asahi-Intec, Biomedical Solutions, Daiichi-Sankyo, Medtronic, and Stryker. Inoue reports personal fees from Daiichi-Sankyo, Bayer, BMS, and Medtronic. Minematsu reports personal fees and other from Bayer Yakuhin and AstraZeneca, personal fees from Otsuka Pharmaceutical, NBI, Mitsubishi Tanabe Pharma, BMS, Pfizer, Japan Stryker, Daiichi-Sankyo, Astellas Pharma, Nippon Chemiphar, and Fuji Film RI Pharma; and other (Advisory Board) from CSL Behring, Medico’s Hirata, EPS Corporation, HEALIOS K.K., and T-PEC Corporation. Koga reports honoraria from Bayer Yakuhin, Otsuka, Daiichi-Sankyo, and NBI, scientific advisory board from Ono, and research support from Takeda, Daiichi-Sankyo, NBI, and Shionogi.None of the other authors has any conflicts of interest to declare. Ethical Approval: The study design followed PRISMA guidelines for IPD systematic reviews. Ethical approval to perform the present IPD analysis was obtained from the site of the corresponding author. The study is registered with PROSPERO (CRD42020213857).

Introduction It is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients. Patients and Methods We conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve. Results A total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training ( n = 1553) and test ( n = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852; p = 0.276 for the Hosmer--Lemeshow test). Discussion and Conclusion Our nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.

Background Malignant profiles were identified by imaging profiles and unfavorable outcomes that have poor response to reperfusion therapy. Many trials have used this profile in their inclusion criteria including large‐vessel occlusion acute ischemic stroke trials. We aimed to redefine the cutoff values for malignant profile in acute ischemic stroke patients with large‐vessel occlusion regardless of reperfusion therapy. Methods and Results Consecutive acute ischemic stroke patients with anterior large‐vessel occlusion were prospectively extracted from the National Cerebral and Cardiovascular Center Stroke Registry between March 2014 and December 2017. Diffusion‐Weighted Imaging‐Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) and diffusion‐weighted imaging lesion ischemic core volume (Vol DWI ) were measured in acute ischemic stroke patients with large‐vessel occlusion with or without treatment. Unfavorable outcome was defined as a modified Rankin Scale score 5 to 6 at 3 months, and optimal DWI ‐ ASPECTS and Vol DWI for unfavorable outcome were assessed. In total, 198 patients (111 men, 77±13 years old) were enrolled. Median DWI ‐ ASPECTS was 7 (5‐9), and median Vol DWI was 55 (6‐134) mL . Among the patients, 72 (36%) patients underwent reperfusion therapy, and 83 (42%) had unfavorable outcomes. The threshold values for a malignant profile on receiver operating characteristic curve analysis for DWI ‐ ASPECTS and Vol DWI were 4 (area under the curve 0.78, P P Conclusions The cutoff values for our redefined malignant profile were DWI ‐ ASPECTS 4 and Vol DWI 71 mL with no selection bias for reperfusion therapy in the real‐world clinical practice. Clinical Trial Registration URL : http://www.clinicaltrials.gov Unique identifier: NCT 02251665

The patient was a 58-year-old man, who was hospitalized with progressive bilateral leg weakness, and sensory impairment in all four extremities. Chronic inflammatory demyelinating polyneuropathy (CIDP) was suspected based on an electrophysiological examination, and intravenous immunoglobulin therapy (IVIg) was initiated. However, his symptoms progressed. The serum and cerebrospinal fluid were positive for human T-lymphotropic virus type 1 (HTLV-1) antibodies; hence the patient was diagnosed as having HTLV-1 associated neuropathy. After administration of corticosteroid, muscle strength markedly improved. Thus, our findings suggest that rather than IVIg, corticosteroid therapy is recommended for the treatment of CIDP like neuropathy in HTLV-1 infected patients.

BACKGROUND Seasonal variations in the severity and outcomes of stroke remain unclarified.Methods and Results:A total of 2,965 acute ischemic stroke patients from a single-center prospective registry were studied. Among the total patients, stroke onset did not vary by season, though it varied with a peak in winter when limited to patients >75 years old (P=0.026), when limited to patients with moderate-to-severe initial neurological deficits (National Institutes of Health Stroke Scale Score ≥10, P=0.014), and when limited to those with cardioembolic stroke (n=1,031, P=0.010). In 1,934 patients with noncardioembolic stroke, stroke onset did not vary by season. After multivariable adjustment, moderate-to-severe neurological deficits were more common in winter (odds ratio 1.37, 95% confidence interval 1.10-1.72) and spring (1.27, 1.01-1.60), and death at 1 year was more common in summer than in fall (1.55, 1.03-2.36); death or dependency (modified Rankin Scale score 3-6) and death or bedridden (score of 5-6) were not differently common among the seasons. CONCLUSIONS Overall ischemic stroke showed a fairly even distribution among the 4 seasons. Cardioembolic stroke was more common in winter. Ischemic stroke patients had more moderate-to-severe initial neurological deficits in winter and spring. Poor clinical outcomes at 1 year were generally similar among the seasons. Ischemic stroke is not necessarily a winter-dominant disease.

Objective:To investigate the relationship between acute perfusion-weighted imaging (PWI) lesions occurring within the first hours after a TIA or a minor brain infarction (BI) and the incidence of new BI detected on a systematic MRI at 1 week.Methods:Consecutive patients who experienced a TIA or BI with a neurologic deficit that lasted Results:Sixty-four patients met the inclusion criteria. Median (IQR) ABCD2 score was 4 (3–5). Median delay from onset to baseline and follow-up MRI was 5 (2–10) hours and 6 (5–7) days, respectively. MRI revealed an acute ischemic lesion on DWI and/or PWI in 38 patients. Nine patients (14%) had a new infarction on follow-up MRI. Each had a PWI and 4 had a DWI lesion on baseline MRI. All new BIs except one were asymptomatic and in the same location as the acute PWI lesion.Conclusions:Our results showed that 30% of the acute focal PWI lesions detected after a TIA are associated with a new BI at 1 week. Those new BIs may result from the progression of the initial ischemic injury.

The patient was a 36-year-old man. His initial symptom was bilateral thigh and calf pain. When he developed ulcerative colitis in the following year, he also noticed wasting of the calf muscles. The clinical feature is similar to gastrocnemius myalgia syndrome, although the left upper limb was also involved. A high-intensity lesion in the left calf and soleus muscles was observed on MRI, which was lead to the diagnosis of non-granulomatous myositis with infiltration of CD68-positive cells based on muscle biopsy. After steroids were administered, his pain subsided. Evaluation with needle EMG, MRI, and muscle biopsy is important when muscle pain accompanies inflammatory bowel disease.