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Abstract 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.

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.

Abstract 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.

Background The effectiveness of endovascular thrombectomy (EVT) has been proven even in patients with large cerebral infarction in the early time window. However, the association of the time course with the treatment effect is unknown. The aim of this analysis was to evaluate the influence of the time course from stroke onset to reperfusion on the therapeutic effect of EVT. Methods The subjects were patients with occlusion of large vessels and sizable strokes on imaging (Alberta Stroke Program Early Computed Tomographic score 3–5) in RESCUE–Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism–Japan Large Ischemic Core Trial), a multicenter, randomized, clinical open‐label trial of EVT versus medical care alone. In the current analysis, the clinical and time course characteristics associated with a favorable outcome (modified Rankin scale [mRS] score of 0–2 and 0–3 at 90 days) were examined in patients treated with EVT. Results The analysis included 71 patients (median age, 77 years; median National Institutes of Health Stroke Scale score on admission, 21). Occlusion sites were the internal carotid artery (48%), proximal segment of the middle cerebral artery (72%) and tandem lesions (20%). Of these patients, 23 (32%) had an mRS score of 0 to 3 and 12 (17%) had an mRS score of 0 to 2 at 90 days. In multivariate analysis, there were independent associations of onset to reperfusion time (odds ratio [OR], 0.991 [95% CI, 0.984–0.999]; P=0.01) and puncture to reperfusion time (OR , 0.952 [95% CI, 0.917–0.988]; P

Background Hemorrhagic transformation after recanalization is a severe complication in patients with a large ischemic core due to cerebral large vessel occlusion. Risk assessment using perfusion imaging to predict hemorrhagic infarction has not been established. Thus, we aimed to investigate the association between perfusion imaging findings and hemorrhagic transformation in patients with acute cerebral large vessel occlusion who had undergone preoperative perfusion imaging evaluation and mechanical thrombectomy. Methods We enrolled consecutive patients who received mechanical thrombectomy after undergoing perfusion imaging for anterior large vessel occlusion from May 2019 to March 2022. The patients in whom recanalization were not achieved and who experienced procedure‐related bleeding were excluded. We investigated the predictors of symptomatic intracranial hemorrhage (sICH) by exploring preoperative perfusion imaging parameters (relative cerebral blood flow, relative cerebral blood volume, time of maximum concentration, and hypoperfusion index ratio). Results Among the 167 patients (median age 79 years, 47% female) enrolled, 63 (38%) and 14 (8%) patients had any intracranial hemorrhage and sICH (sICH group), respectively. The sICH group had a shorter puncture‐recanalization time than the non‐sICH group (median [interquartile range (IQR)]; 43 [34–55] versus 61 [37–88]; P=0.046), whereas the modified Rankin scale at 90 days showed a worse prognosis (median [IQR]; 5 [5–6] versus 3 [1–4]; P

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.

Background We investigated the impact of the ring finger protein 213 p.R4810K variant, a founder variant for moyamoya disease in East Asians, on endovascular therapy outcomes in patients with acute anterior‐circulation large‐vessel occlusion stroke in comparison with noncarriers. Methods Of the consecutive patients with ischemic stroke admitted to our institute from 2011 to 2021, patients who underwent endovascular therapy for acute occlusion of the intracranial internal carotid artery or M1 segment of the middle cerebral artery were included. Outcomes were instant reocclusion, final modified Thrombolysis in Cerebral Infarction reperfusion ≥2b, and early reocclusion. Instant reocclusion was defined as the occurrence of reocclusion during the procedure, and early reocclusion was defined as reocclusion detected on magnetic resonance angiography within 2 weeks after the confirmation of successful reperfusion. Results Of the 277 patients analyzed (128 women; median age, 76 years), 10 patients (3.6%) carried the ring finger protein 213 p.R4810K variant. Variant carriers were younger (P=0.01) and more frequently had intracranial atherosclerotic disease‐related large‐vessel occlusion as a cause of acute large‐vessel occlusion (P

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.

The benefits of mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) and a large ischemic core (LIC) at presentation are uncertain. We aimed to obtain up-to-date aggregate estimates of the outcomes following MT in patients with volumetrically assessed LIC. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-conformed, PROSPERO-registered, systematic review and meta-analysis of studies that included patients with AIS and a baseline LIC treated with MT, reported ischemic core volume quantitatively, and included patients with a LIC defined as a core volume ≥50 mL. The search was restricted to studies published between January 2015 and June 2020. Random-effects-meta-analysis was used to assess the effect of MT on 90-day unfavorable outcome (i.e., modified Rankin Scale [mRS] 3–6), mortality, and symptomatic intracranial hemorrhage (sICH) occurrence. Sensitivity analyses were performed for imaging-modality (computed tomography-perfusion or magnetic resonance-diffusion weighted imaging) and LIC-definition (≥50 or ≥70 mL). We analyzed 10 studies (954 patients), including six (682 patients) with a control group, allowing to compare 332 patients with MT to 350 who received best-medical-management alone. Overall, after MT the rate of patients with mRS 3–6 at 90 days was 74% (99% confidence interval [CI], 67 to 84; Z-value=7.04; I2=92.3%) and the rate of 90-day mortality was 36% (99% CI, 33 to 40; Z-value=–7.07; I2=74.5). Receiving MT was associated with a significant decrease in mRS 3–6 odds ratio (OR) 0.19 (99% CI, 0.11 to 0.33; P

Background We retrospectively compared early‐ (

Introduction: The ring finger protein 213 gene (RNF213) has been identified as a susceptibility gene for moyamoya disease, and the p.R4810K polymorphism as a founder variant commonly found in East Asian patients. 1 A recent large case‐control study including over 46,958 Japanese subjects reported that the RNF213 p.R4810K variant was a strong risk factor for Japanese cerebral infarction: the variant was found in 5.2% of patients with non‐cardioembolic stroke and in 2.1% of healthy controls. 2 Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke due to occlusion of the internal carotid artery and M1 segment of the middle cerebral artery, but in East Asians, about 15–25% of LVOs for which MT was performed were reportedly caused by intracranial atherosclerotic disease (ICAD). 3 RNF213 p.R4810K variant may be involved to some extent in ICAD‐related LVO of Asian patients undergoing MT. In this study, we aimed to investigate the impact of RNF213 p.R4810K variant on EVT for anterior circulation LVO stroke. Methods: Of the consecutive ischemic stroke patients from 2011 to 2021 seen in our institute, patients who underwent EVT for acute occlusion of the intracranial ICA or M1 segment of MCA and signed a consent form for RNF213 genotyping were included. Outcomes were instant re‐occlusion, final modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b reperfusion, early re‐occlusion, and modified Rankin Scale (mRS) score 0–2 at 90 days. Instant re‐occlusion was defined as occurrence of re‐occlusion during the procedure, whereas early re‐occlusion as re‐occlusion detected on magnetic resonance angiography within 2 weeks after confirmation of successful reperfusion at the end of the procedure. 4 Results: Of the 277 patients (128 women [46.2%]; median age, 76 years) analyzed, 10 (3.6%) patients had the RNF213 p.R4810K variant. The variant carriers were younger (67 years vs. 76 years, P

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.

Introduction: The usefulness of the blind exchange with mini-pinning (BEMP) technique has recently been reported for mechanical thrombectomy in patients with stroke owing to medium vessel occlusion (MeVO). The Tron stent retriever can be delivered and deployed through a 0.0165-inch microcatheter. This retriever has potential as an effective and safe treatment for acute ischemic stroke (AIS) due to occlusion of the M2 segment of the middle cerebral artery (MCA). Here, we report the outcomes of the BEMP technique using Tron stent retrievers for M2 occlusion thrombectomy.Methods: Consecutive patients with AIS owing to M2 occlusion who underwent the BEMP technique using 2 × 15-mm or 4 × 20-mm Tron stent retrievers were included. The technique involves deploying a Tron stent retriever through a 0.0165-inch microcatheter, followed by microcatheter removal and blind navigation of a 3MAX or 4MAX aspiration catheter over the bare Tron delivery wire until the aspiration catheter reaches the clot. A Tron stent retriever is inserted into the aspiration catheter like a cork and subsequently pulled as a unit. We assessed procedural outcomes [first-pass expanded thrombolysis in cerebral infarction (eTICI) score 2c/3 and 2b/2c/3], safety outcomes [symptomatic intracranial hemorrhage (sICH)], and clinical outcomes (good outcome rate defined as modified Rankin Scale score 0–2 at 90 days and mortality at 90 days).Results: Eighteen M2 vessels were treated in 15 patients (six female, median age: 80 years, and median National Institutes of Health Stroke Scale score: 18). The BEMP technique was performed successfully in all cases. Whether to use a 3MAX or 4MAX catheter was determined by considering one of the following target vessels: dominant, non-dominant, or co-dominant M2 (3MAX, n = 9; 4MAX, n = 9). The first-pass eTICI 2c/3 and 2b/2c/3 rates were 47 (7/15) and 60% (9/15), respectively; sICH was not observed. Seven patients (47%) achieved good outcomes, and one patient (7%) died within 90 days.Conclusions: The Tron stent retriever was safely and effectively used in the BEMP technique for acute MCA M2 occlusion and can be combined with a 0.0165-inch microcatheter, which may be useful for treating MeVO, in general.

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.

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 (VolDWI) 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 VolDWI 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 VolDWI 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 VolDWI were 4 (area under the curve 0.78, P

Abstract Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.

Objective: Patients with motor neuron disease rarely present with fasciculation which is large enough to be clinically recognized as myoclonus. This study is aimed at elucidating the features of large fasciculation manifesting as myoclonus by using surface electromyography (surface EMG) and dynamic echomyography (dynamic Echo). Methods: Four patients with amyotrophic lateral sclerosis, two of whom clinically presented with both fasciculation and myoclonus, were studied by using the surface EMG and the dynamic Echo. Results: At rest, all patients had fasciculation in atrophic muscles, and the surface EMG showed occasional discharges of different waveforms corresponding to fasciculation. During voluntary gentle muscle contraction, the surface EMG showed repetitive discharges in the contracting muscle, which were constant in size and waveform within each muscle. The muscle Echo at rest revealed occasional contractions of a small number of muscle fibers corresponding to fasciculation. During voluntary muscle contraction, the number of muscle fibers involved in the involuntary motor phenomena was larger in the patients who clinically presented with myoclonus compared with other patients who clinically presented only with fasciculation. In a patient who presented with myoclonus, there was no contraction in the antagonist muscle. Conclusions: Fasciculation involving a large number of muscle fibers clinically manifests as spinal myoclonus. Significance: Fasciculation involving a large number of muscle fibers can be a cause of spinal myoclonus. Keywords: Large fasciculation, Spinal myoclonus, Motor neuron disease, Dynamic echomyography, Surface electromyography

Background We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio (INR)

BackgroundThe crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form.Methods and findingsHospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (PConclusionsThe rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.

Objective: This paper reports a patient with bulbospinal muscular atrophy (BSMA) who presented with spinal myoclonus, documented by video and surface electromyography. Case report: A 66-year-old man had progressive gait disturbance, dysphagia, and easy fatigability of all extremities over a period of 4 years. Neurologically, muscle atrophy, fasciculation, and weakness were observed in the bulbar and limb muscles. When the knees were kept in mild flexion in the supine position, fasciculation of the thigh adductor muscles was so large that it caused shock-like involuntary movements of the legs, corresponding to spinal myoclonus. A genetic test revealed 41 repeats of CAG in the androgen receptor gene, and the diagnosis of BSMA was made. Significance: The present case suggests that extremely large fasciculation can cause spinal myoclonus. Keywords: Fasciculation, Spinal myoclonus, Motor neuron disease, Bulbospinal muscular atrophy, Surface electromyography

BackgroundThe purpose of this study was to examine the relationships between glucose parameters obtained by continuous glucose monitoring and clinical outcomes in acute stroke patients. Methods and ResultsConsecutive patients with acute ischemic stroke or intracerebral hemorrhage within 24 hours after onset were included. A continuous glucose monitoring device (iPro2) was attached for the initial 72 hours after emergent admission. Eight glucose parameters were obtained from continuous glucose monitoring: maximum, minimum, mean, and SD of blood glucose levels, as well as area under the curve more than 8 mmol/L of blood glucose, distribution time more than 8 mmol/L of blood glucose, coefficient of variation (%CV), and presence of time less than 4 mmol/L over 72 hours. The primary outcome measure was death or dependency at 3 months (modified Rankin Scale score ≥3). One hundred patients with acute ischemic stroke (n=58) or intracerebral hemorrhage (n=42) were included. Blood glucose levels varied between 5.2±1.4 and 11.4±3.2 mmol/L over 72 hours, with area under the curve more than 8 mmol/L of blood glucose of 0.7±1.4 min×mmol/L, distribution time more than 8 mmol/L of blood glucose of 31.7±32.7%, coefficient of variation of 15.5±5.4%, and presence of hypoglycemia in 20% of overall patients. Mean glucose level (adjusted odds ratio, 1.60, 95% confidence interval, 1.12–2.28/1 mmol/L), area under the curve more than 8 mmol/L of blood glucose (2.13, 1.12–4.02/1 min×mmol/L), and distribution time more than 8 mmol/L of blood glucose (1.25, 1.05–1.50/10%) were related to death or dependency for overall patients, as well as for acute ischemic stroke patients (2.05, 1.15–3.65; 2.38, 1.04–5.44; 1.85, 1.10–3.10, respectively). ConclusionsHigh mean glucose levels, distribution time more than 8 mmol/L of blood glucose, and areas under the curve more than 8 mmol/L of blood glucose during the initial 72 hours of acute stroke were associated with death or dependency at 3 months.

Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya.We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4-9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0-17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment.Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies.

BACKGROUND: A strategy to combat infectious diseases, including neglected tropical diseases (NTDs), will depend on the development of reliable epidemiological surveillance methods. To establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in Kenya. METHODS: We developed a microsphere-based immuno-assay system to simultaneously measure the individual levels of plasma antibody (IgG) against 8 antigens derived from 6 pathogens: Entamoeba histolytica (C-IgL), Leishmania donovani (KRP42), Toxoplasma gondii (SAG1), Wuchereria bancrofti (SXP1), HIV (gag, gp120 and gp41), and Vibrio cholerae (cholera toxin). The assay system was validated using appropriate control samples. The assay system was applied for 3411 blood samples collected from the general population randomly selected from two health and demographic surveillance system (HDSS) cohorts in the coastal and western regions of Kenya. The immunoassay values distribution for each antigen was mathematically defined by a finite mixture model, and cut-off values were optimized. FINDINGS: Sensitivities and specificities for each antigen ranged between 71 and 100%. Seroprevalences for each pathogen from the Kwale and Mbita HDSS sites (respectively) were as follows: HIV, 3.0% and 20.1%; L. donovani, 12.6% and 17.3%; E. histolytica, 12.8% and 16.6%; and T. gondii, 30.9% and 28.2%. Seroprevalences of W. bancrofti and V. cholerae showed relatively high figures, especially among children. The results might be affected by immunological cross reactions between W. bancrofti-SXP1 and other parasitic infections; and cholera toxin and the enterotoxigenic E. coli (ETEC), respectively. INTERPRETATION: A microsphere-based multi-serological assay system can provide an opportunity to comprehensively grasp epidemiological features for NTDs. By adding pathogens and antigens of interest, optimized made-to-order high-quality programs can be established to utilize limited resources to effectively control NTDs in Africa.

Infection and transmission of multidrug-resistant Mycobacterium tuberculosis (MDR-Mtb) and extensively drug-resistant M. tuberculosis (XDR-Mtb) is a serious health problem. We analyzed a total of 1,110 Mtb isolates in Osaka Prefecture and neighboring areas from April 2000 to March 2009. A total of 89 MDR-Mtb were identified, 36 (48.5%) of which were determined to be XDR-Mtb. Among the 89 MDR-Mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on mycobacterial interspersed repetitive units-various number of tandem repeats (MIRU-VNTR) typing. Among these six clusters, the MIRU-VNTR patterns of four (OM-V02, OM-V03, OM-V04, and OM-V06) were only found for MDR-Mtb. Further analysis revealed that all isolates belonging to OM-V02 and OM-V03, and two isolates from OM-V04 were clonal. Importantly such genotypes were not observed for drug-sensitive isolates. These suggest that few but transmissible clones can transmit after acquiring multidrug resistance and colonize even in a country with a developed, well-organized healthcare system.