Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

BACKGROUND: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. METHODS: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. RESULTS: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively (P=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (P=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. CONCLUSIONS: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

OBJECTIVE: The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. METHODS: We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. RESULTS: The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P = 0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P = 0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P = 0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P = 0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P < 0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P < 0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P = 0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P < 0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P = 0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P = 0.164). CONCLUSIONS: In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Magnetic Resonance Imaging-Guided Intravenous Thrombolysis in Cardioembolic Stroke Patients With Unknown Time of Onset　- Subanalysis of the THAWS Randomized Control Trial.

BACKGROUND: We investigated the clinical effect of intravenous thrombolysis using a magnetic resonance imaging (MRI)-guided approach in cardioembolic stroke (CE) patients with unknown time of onset.Methods and Results: This subanalysis of the THAWS trial assessed the efficacy and safety of alteplase 0.6 mg/kg in CE patients with unknown time of onset and showing diffusion-weighted imaging-fluid-attenuated inversion recovery mismatch. Patients were classified as CE and non-CE using the SSS-TOAST classification system during the acute period. The efficacy outcome was a modified Rankin Scale score of 0-1 at 90 days. In all, 126 patients from the THAWS trial were included in this study, of whom 45 (35.7%) were diagnosed with CE. In the CE group, a favorable outcome was numerically more frequent in the alteplase than control group (52% vs. 35%; adjusted odds ratio [aOR] 2.25; 95% confidence interval [CI] 0.50-9.99). However, in the non-CE group, favorable outcomes were comparable between the alteplase and control groups (44% vs. 55%, respectively; aOR 0.39; 95% CI 0.12-1.21). Treatment-by-cohort interaction for a favorable outcome was modestly significant between the CE and non-CE groups (P=0.069). In the CE group, no patients experienced symptomatic intracranial hemorrhage (ICH) or parenchymal hematoma Type II following thrombolysis. CONCLUSIONS: When an MRI-guided approach is used, CE patients with unknown time of onset appear to be suitable candidates for thrombolysis.

Association between diet quality and risk of stunting among school-aged children in Schistosoma mansoni endemic area of western Kenya: a cross-sectional study.

BACKGROUND: Healthy eating habits are essential for improving nutritional status and strengthening immunity against infectious diseases. This study examined the relationship between diet quality and stunting in school-aged children in an infectious disease-endemic area of western Kenya. METHODS: This cross-sectional study included 260 school-aged children (age 9-17 years) enrolled in primary schools in Mbita Sub-county, western Kenya. The nutritional status was assessed using anthropometric measurements. Dietary intake was measured using food frequency questionnaires and evaluated using the Food Pyramid (FP) score, which indicates adherence to the Kenyan food-based dietary guideline. Information on the children's age, sex, maternal education, and household wealth index was collected using a household-based questionnaire. Infections with the predominant parasites, such as Schistosoma (S.) mansoni, were detected via microscopy. The trend associations of the FP score with food group intake were examined to characterize the dietary intake of this population. Logistic regression analysis was performed to investigate the relationship between stunting and FP score tertiles, adjusted for sociodemographic and economic indicators and parasitic infection status. RESULTS: Among the studied schoolchildren, 15.0% exhibited stunting, while 76.2% were infected with S. mansoni. The mean FP score was 25.6 out of 50 points. A higher FP score was characterized by a high intake of roots and tubers, dairy products, pulses, and fruits and a low intake of cereals and animal-source foods. The analysis revealed a trend: a lower risk of stunting was evident in groups with elevated FP scores (p for trend = 0.065). However, these trend associations were observable among subjects with either negative or light S. mansoni infection (p for trend = 0.016). CONCLUSIONS: A higher quality diet, as evaluated by FP scores, was associated with a low risk of stunting among school-aged children. Notably, this association seemed to weaken in the presence of a high burden of S. mansoni infection. It highlights the importance of enhancing dietary quality through the promotion of diverse nutrient-dense foods alongside effective S. mansoni infection control for improved growth. This study contributes fundamental knowledge for understanding the diet-malnutrition relationship in areas endemic for S. mansoni infection.

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.

Intravenous alteplase before endovascular therapy for acute large vessel occlusion with large ischemic core: subanalysis of a randomized clinical trial.

BACKGROUND: The efficacy of endovascular therapy (EVT) in patients with large ischemic core has been reported, but it remains unclear whether IV alteplase (IVT) has beneficial effects in addition to EVT in such patients. We evaluated the efficacy and safety of EVT with or without IVT. METHODS: The RESCUE-Japan LIMIT was an open-label, prospective, multicenter, randomized clinical trial to evaluate the efficacy and safety of EVT in stroke patients with large ischemic core, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5. This subanalysis evaluated the differences in the effects of EVT with medical care (EVT group) compared with medical care alone (No-EVT group) between those who received IVT (IVT stratum) and those who did not (No-IVT stratum) before EVT. RESULTS: Among 202 enrolled patients, 147 (73%) did not receive IVT. In the No-IVT stratum, the modified Rankin Scale (mRS) score of 0-3 at 90 days was significantly higher in the EVT group than in the No-EVT group (31.1% vs 12.3%, OR 3.21 (95% CI 1.37 to 7.53)). In the IVT stratum, the mRS score of 0-3 was 30.8% in the EVT group and 13.8% in the No-EVT group (OR 2.78 (95% CI 0.72 to 10.7)) (interaction p=0.77). The incidence of symptomatic intracranial hemorrhage was not different between the two groups in the No-IVT stratum (OR 1.20 (95% CI 0.35 to 4.12)), but it was significantly higher in the EVT group than in the No-EVT group in the IVT stratum (11.5% vs 0%, p=0.03). CONCLUSIONS: There was no difference in efficacy of EVT with or without IVT, while IVT before EVT might increase symptomatic intracranial hemorrhage in patients with large ischemic core. TRIAL REGISTRATION INFORMATION: NCT03702413.

Mode of Imaging Study and Endovascular Therapy for a Large Ischemic Core: Insights From the RESCUE-Japan LIMIT.

BACKGROUND AND PURPOSE: Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core. METHODS: The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan-Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3-5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum. RESULTS: Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65-2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46-16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008). CONCLUSION: Patients with ASPECTS of 3-5 on MRI benefitted more from EVT than those with ASPECTS of 3-5 on CT.

[A case of total hip arthroplasty for femoral head necrosis while using satralizumab for neuromyelitis optica spectrum disorders].

A 47-year-old woman developed right femoral head necrosis during long-term steroid use for neuromyelitis optica spectrum disorder. She underwent a total hip arthroplasty because her right hip pain persisted after satralizumab treatment. There were no postoperative infections. Under oral administration of tacrolimus 3 mg, prednisolone 11 mg, and acetaminophen 2,275 mg, her postoperative body temperature was less than 38°C and normalized in about 2 days after the operation. No parameters indicating worsening of inflammation were observed in the blood test. In satralizumab-treated patients, infection cannot be ruled out even without inflammatory findings. In particular, if a slight fever of the 37°C-range or a mildly high white blood cell count persists, paying attention to signs of infection and actively investigating the presence or absence of infection using medical image diagnostic devices are necessary.

Number of Passes of Endovascular Therapy for Stroke With a Large Ischemic Core: Secondary Analysis of RESCUE-Japan LIMIT.

BACKGROUND: The increased risk of intracranial hemorrhage with multiple passes in endovascular therapy (EVT) for large vessel occlusion with a large ischemic core is a concern. We explored the effect of the number of EVT passes on patients in a randomized clinical trial. METHODS: This post hoc study was the secondary analysis of RESCUE-Japan LIMIT, which was a randomized clinical trial comparing EVT and medical treatment alone for large vessel occlusion with large ischemic core. We grouped patients according to the number of passes with successful reperfusion (modified Thrombolysis in Cerebral Infarction score, ≥2b) in 1, 2, and 3 to 7 passes and failed reperfusion (modified Thrombolysis in Cerebral Infarction score, 0-2a) after any pass in the EVT group, and these groups were compared with medical treatment group. The primary outcome was modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were improvement in National Institutes of Health Stroke Scale score of ≥8 at 48 hours, mortality at 90 days, symptomatic intracranial hemorrhage, and any intracranial hemorrhage within 48 hours. RESULTS: The number of patients who received EVT with successful reperfusion after 1, 2, and 3 to 7 passes and failed reperfusion were 44, 23, 19, and 14, respectively, and 102 received medical treatment alone. The adjusted odds ratios (95% CIs) for the primary outcome relative to medical treatment were 5.52 (2.23-14.28) after 1 pass, 6.45 (2.22-19.30) after 2 passes, 1.03 (0.15-4.48) after 3 to 7 passes, and 1.17 (0.16-5.37) if reperfusion failed. The adjusted odds ratios (95% CIs) for any intracranial hemorrhage within 48 hours relative to medical treatment were 1.88 (0.90-3.93) after 1 pass, 5.14 (1.97-14.72) after 2 passes, 3.00 (1.09-8.58) after 3 to 7 passes, and 6.16 (1.87-24.27) if reperfusion failed. CONCLUSIONS: The successful reperfusion within 2 passes was associated with better clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03702413.

Tmax Mismatch Ratio to Identify Intracranial Atherosclerotic Stenosis-Related Large-Vessel Occlusion Before Endovascular Therapy.

Background We aimed to clarify which time-to-maximum of the tissue residue function (Tmax) mismatch ratio is useful in predicting anterior intracranial atherosclerotic stenosis (ICAS)-related large-vessel occlusion (LVO) before endovascular therapy. Methods and Results Patients with ischemic stroke who underwent perfusion-weighted imaging before endovascular therapy for anterior intracranial LVO were divided into those with ICAS-related LVO and those with embolic LVO. Tmax ratios of >10 s/>8 s, >10 s/>6 s, >10 s/>4 s, >8 s/>6 s, >8 s/>4 s, and >6 s/>4 s were considered Tmax mismatch ratios. Binominal logistic regression was used to identify ICAS-related LVO, and the adjusted odds ratio (aOR) and 95% CI for each Tmax mismatch ratio increase of 0.1 were calculated. A similar analysis was performed for ICAS-related LVO with and without embolic sources, using embolic LVO as the reference. Of 213 patients (90 women [42.0%]; median age, 79 years), 39 (18.3%) had ICAS-related LVO. The aOR (95% CI) per 0.1 increase in Tmax mismatch ratio in ICAS-related LVO with embolic LVO as reference was lowest with Tmax mismatch ratio >10 s/>6 s (0.56 [0.43-0.73]). Multinomial logistic regression analysis also showed the lowest aOR (95% CI) per 0.1 increase in Tmax mismatch ratio with Tmax >10 s/>6 s (ICAS-related LVO without embolic source: 0.60 [0.42-0.85]; ICAS-related LVO with embolic source: 0.55 [0.38-0.79]). Conclusions A Tmax mismatch ratio of >10 s/>6 s was the optimal predictor of ICAS-related LVO compared with other Tmax profiles, with or without an embolic source before endovascular therapy. Registration clinicaltrials.gov. Identifier NCT02251665.

Atrial Fibrillation Detected before or after Stroke: Role of Anticoagulation.

BACKGROUND: Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk. METHODS: Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation. RESULTS: Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death. CONCLUSION: Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54.

Rapid Evaluation of Large Vessel Occlusion for Mechanical Thrombectomy Using Carotid Duplex Ultrasound.

Objectives This study clarified the usefulness of carotid duplex ultrasound (CDU) in evaluating large vessel occlusion (LVO) in patients with acute stroke planned to be treated with mechanical thrombectomy (MT). Methods This study was single-center, prospective, observational trial. If the ratio of end-diastolic velocity in the common carotid arteries was ≥1.4, or diastolic flow in the affected internal carotid artery (ICA) was absent on CDU, patients were immediately transferred to the angio-suite without additional cerebrovascular imaging. Clinical parameters, including time metrics and outcomes, were evaluated in participants. Patients We enrolled stroke patients with a National Institutes of Health Stroke Scale score ≥6 and Alberta Stroke Program Early CT score ≥6 in whom MT could be initiated within 6 hours of the stroke onset. Results Among 140 patients screened during the study period, 48 were ultimately enrolled. Twenty-seven patients were diagnosed with LVO by CDU alone. CDU offered 83% sensitivity and 82% specificity for identifying the occlusion of the ICA or M1 segment of the middle cerebral artery. Among the 29 total patients treated with MT, 20 (67%) showed a modified Rankin Scale score ≤2 at 90 days. The door-to-puncture time was significantly shorter in patients evaluated by CDU alone (34 minutes) than in those evaluated by magnetic resonance angiography after CDU (47.5 minutes, p<0.001). Conclusion CDU might reduce the time metrics for early initiation of MT with good sensitivity and specificity in identifying LVO.

Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure?

BACKGROUND: Some patients with even T2 low rectal cancer are known to develop lateral pelvic lymph node metastasis. This study aimed to investigate real-world evidence regarding lateral nodal metastasis on T2 low rectal cancer treatment. METHODS: Consecutive patients with pathological T2 low rectal adenocarcinoma who underwent curative-intent surgery between January 2007 and December 2015 at two Japanese cancer centres dedicated to lateral pelvic lymph node dissection were identified and included in the analysis. Lateral pelvic lymph node metastasis was defined as pathologically confirmed metastatic lateral pelvic lymph node or lateral-local recurrence after primary surgery. RESULTS: A total of 215 consecutive patients, including 101 and 114 patients who did and did not undergo bilateral lateral pelvic lymph node dissection, were included in the analysis. Overall, 19 (8.8%) patients had lateral pelvic lymph node metastasis, including 13 with pathologically confirmed metastatic lateral pelvic lymph node and six with lateral-local recurrence. A total of 10 (4.7%) patients had local recurrence, including six with lateral-local recurrence, two with central-local recurrence and two with anastomotic recurrence. Five/7-year cumulative risks of lateral-local recurrence in patients with and without lateral pelvic lymph node dissection were 1.1/1.1% and 3.9/5.2%, respectively. CONCLUSION: The problem of the relatively high rate of lateral local recurrence remains in treating T2 low rectal cancer with only total mesorectal excision. The selection of high-risk patients of lateral pelvic lymph node metastasis and the indication of additional treatment in T2 low rectal cancer should be discussed further.

Lateral medullary infarction presenting only with dermatomal sensory disturbance: a case report.

The triad of Horner's syndrome, ataxia and sensory disturbances clinically identifies patients with lateral medullary infarct (LMI). However, dermatomal temperature and pain sensory loss have rarely been reported in patients with LMI. We describe the case of a patient with LMI presenting solely with temperature and pain sensory disorder below the C5 sensory level. Magnetic resonance imaging findings demonstrated a small superficial infarction in the right lateral medulla oblongata, indicating that the sensory deficit was caused by a restricted infarction of the lateral spinothalamic tract. We emphasize the importance of adding LMI to a differential diagnosis of acute dermatomal sensory disturbance without other major symptoms of LMI, such as cranial nerve abnormalities, ataxia and Horner's syndrome.

Safety outcomes of early initiation of antithrombotic agents within 24 h after intravenous alteplase at 0.6 mg/kg.

BACKGROUND: We examined outcome of acute ischemic stroke (AIS) with administration of antithrombotics within 24 h after intravenous low-dose alteplase. METHODS: Consecutive AIS patients who were treated with intravenous alteplase at 0.6 mg/kg from 2005 to 2021 were retrospectively included in our single-center registry. Patients were classified into two groups: those who received antithrombotics within 24 h after intravenous alteplase (early initiation group) and those who did not (control group). Safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH (sICH) within 36 h after onset, and death within 3 months. sICH was defined as any ICH with a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or death within 36 h. RESULTS: Of 1111 patients (women, 426; median age, 76 [interquartile range, 69-83] years; median NIHSS score, 11 [6-19]; cardioembolism, 580 [52.2%]), early initiation group comprised 58 patients (22; 72 [65-80] years; 7 [4-12]; 11 [19.0%]) and control group comprised 1053 patients (404; 77 [69-84] years; 11 [6-19]; 569 [54.1%]). No significant between-group differences were observed in the incidence of any ICH (17.2% vs. 21.6%; adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 0.57-2.44), sICH (0% vs. 0.9%, P = 1.00), or death within 3 months (5.2% vs. 6.7%; aOR, 1.23; 95% CI, 0.36-4.23). CONCLUSIONS: Early initiation of antithrombotics after intravenous alteplase at 0.6 mg/kg did not increase the rate of sICH or death within 3 months and may be used with caution in patients with advanced neurological deterioration.

A review of 14 cases of perianal Paget's disease: characteristics of anorectal cancer with pagetoid spread.

BACKGROUND: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget's disease (PPD) and to explore rational treatment options and follow-up for this disease. METHODS: The National Cancer Center Hospital database was searched for all cases of perianal Paget's disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases. RESULTS: All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1-13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2-81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%. CONCLUSIONS: Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.

Intravenous Alteplase at 0.6 mg/kg for Unknown Onset Stroke with Prior Antithrombotic Medication: THAWS Randomized Clinical Trial.

AIM: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke. METHODS: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication. RESULTS: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication. CONCLUSION: Alteplase appears more beneficial in patients with prior antithrombotic medication.

Plasma mid-regional pro-adrenomedullin: A biomarker of the ischemic penumbra in hyperacute stroke.

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p < 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (rs  = 0.09, p = 0.348), they were higher in HAIS with CDM (n = 34; 0.81 vs. 0.61 nmol/L, p < 0.001) or MDM (n = 26; 0.83 vs. 0.62 nmol/L, p = 0.002). These differences remained significant after adjusting baseline factors (adjusted odds ratio, 4.06 [95% CI, 1.31-12.55], p = 0.015 and 4.65 [1.35-16.11], p = 0.015, respectively). Plasma MR-proADM is elevated in HAIS, especially in those with a substantial penumbra, suggesting potential as a blood biomarker in this region.