Prehospital Notification Using a Mobile Application Can Improve Regional Stroke Care System in a Metropolitan Area.

BACKGROUND: Acute ischemic stroke is a time-sensitive disease. Emergency medical service (EMS) prehospital notification of potential patients with stroke could play an important role in improving the in-hospital medical response and timely treatment of patients with acute ischemic stroke. We analyzed the effects of FASTroke, a mobile app that EMS can use to notify hospitals of patients with suspected acute ischemic stroke at the prehospital stage. METHODS: We conducted a retrospective observational study of patients diagnosed with acute ischemic stroke at 5 major hospitals in metropolitan Daegu City, Korea, from February 2020 to January 2021. The clinical conditions and time required for managing patients were compared according to whether the EMS employed FASTroke app and further compared the factors by dividing the patients into subgroups according to the preregistration received by the hospitals when using FASTroke app. RESULTS: Of the 563 patients diagnosed with acute ischemic stroke, FASTroke was activated for 200; of these, 93 were preregistered. The FASTroke prenotification showed faster door-to-computed-tomography times (19 minutes vs. 25 minutes, P < 0.001), faster door-to-intravenous-thrombolysis times (37 minutes vs. 48 minutes, P < 0.001), and faster door-to-endovascular-thrombectomy times (82 minutes vs. 119 minutes, P < 0.001). The time was further shortened when the preregistration was conducted simultaneously by the receiving hospital. CONCLUSION: The FASTroke app is an easy and useful tool for prenotification as a regional stroke care system in the metropolitan area, leading to reduced transport and acute ischemic stroke management time and more reperfusion treatment. The effect was more significant when the preregistration was performed jointly.

Characteristics of Acute Stroke in Patients with Coronavirus Disease 2019 and Challenges in Stroke Management during an Epidemic.

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic infection associated with high morbidity and mortality. The Korean city of Daegu endured the first large COVID-19 outbreak outside of China. Since the report of the first confirmed case in Daegu on February 18, 2020, a total of 6,880 patients have been reported until May 29, 2020. We experienced five patients with ischemic stroke and COVID-19 during this period in four tertiary hospitals in Daegu. The D-dimer levels were high in all three patients in whom D-dimer blood testing was performed. Multiple embolic infarctions were observed in three patients and suspected in one. The mean time from stroke symptom onset to emergency room arrival was 22 hours. As a result, acute treatment for ischemic stroke was delayed. The present case series report raises the possibility that the coronavirus responsible for COVID-19 causes or worsens stroke, perhaps by inducing inflammation. The control of COVID-19 is very important; however, early and proper management of stroke should not be neglected during the epidemic.

The impact of prior antithrombotic status on cerebral infarction in patients with atrial fibrillation.

BACKGROUND: Anticoagulation effectively prevents cardioembolic stroke in atrial fibrillation (AF) patients, whereas it is less effective than antiplatelet therapy (AT) in noncardioembolic stroke prevention. We hypothesized that the ischemic lesion pattern and vascular patency would differ according to the antithrombotic treatment status in AF patients. METHODS: The medical records of 1078 acute ischemic stroke patients with AF were retrospectively reviewed. Patients were classified according to medication at stroke onset: (1) optimal anticoagulation (OAC; international normalized ratio [INR] 1.7-3.0; n = 36); (2) suboptimal anticoagulation (SOAC; INR ≤1.7; n = 134); (3) AT (n = 285); and (4) control (no antithrombotic medication; n = 623). Imaging and clinical variables of each group were compared with that of controls. RESULTS: Small cortical or single subcortical infarctions were more common in the OAC group than in controls (6% vs. 1% and 22% vs. 8%, respectively; standardized residual, 2.4 and 2.8). Multicirculatory infarctions were less common in the OAC group than in controls (0% vs. 11%; standardized residual, -2.0). Obstruction of the corresponding artery was less common in the OAC group than in controls (26.5% vs. 46.5%, P = .02). Initial neurologic severity was lower in the OAC and AT groups than in controls (P = .01 and .03, respectively). OAC and AT were independently associated with favorable functional outcome at 3-months (P = .015 and <.001, respectively). CONCLUSIONS: Ischemic stroke can occur during OAC in AF patients. Small cortical or single subcortical lesions were more common than typical cardioembolic lesion patterns. OAC and AT were protective against severe neurologic deficit and independently associated with favorable outcome, but SOAC was not.

Patent foramen ovale and infarct volume in cryptogenic stroke.

BACKGROUND: The causal relationship between patent foramen ovale (PFO) and stroke is controversial. We hypothesized that if PFO is a pathway of embolic source, there might be a correlation between PFO characteristics (ie, size or extent of shunt) and ischemic lesion burden (ie, infarct volume and number). METHODS: From ischemic stroke patients admitted to Asan Medical Center between January 2000 and October 2007, we identified those who had (1) acute ischemic lesion on diffusion-weighted imaging within 5 days of symptom onset and (2) cryptogenic stroke and only PFO detected by transesophageal echocardiography. PFO characteristics on echocardiographic studies included size, shunt grade, shunt pattern, and the presence of atrial septal aneurysm (ASA). RESULTS: Enrolled were 75 patients (male, 56%; mean age, 45.3±13.9 years), including 10 patients (13.3%) with ASA. In univariable analysis, PFO size was positively correlated with log-transformed infarct volume (LIV) (regression coefficient=.469, P=.009). After adjusting for hypertension, stroke history, and migraine (all P<.2), PFO size remained independently associated with LIV (regression coefficient=.481, P=.007). Lesion number was negatively correlated with PFO size (Spearman coefficient rho=-.251, P=.03). The initial National Institutes of Health Stroke Scale scores tended to be positively correlated with PFO size (Spearman coefficient rho=.223, P=.054). CONCLUSIONS: In cryptogenic stroke, PFO size and ischemic lesion burden were positively correlated. These results support that PFO may play a role as a pathway of embolic source in cryptogenic stroke.

An isolated pontine infarct extending to the basal pontine surface has a higher abnormal ankle-brachial index.

Patients with ischemic stroke and branch atheromatous disease (BAD) have worse neurological deficits and prognoses than those with small vessel occlusion (SVO). However, both disorders are forms of deep brain infarctions. This study aimed to investigate an MRI-based etiological classification for isolated pontine infarctions and assess differences in vascular risk factors and peripheral arterial disease among etiological subtypes. Consecutive data of patients admitted for acute ischemic stroke or transient ischemic attack between August 2016 and July 2019 were reviewed. Acute isolated pontine infarcts were classified into 3 groups: BAD, SVO, and large-artery atherosclerosis (LAA), according to basilar or vertebral artery steno-occlusion and the extent of the infarct lesion on the basal pontine surface as displayed on magnetic resonance imaging and angiography. Vascular risk factors, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity were analyzed in the 3 groups. Among 64 enrolled patients, BAD was the most common cause of isolated pontine infarct. The BAD group had a higher frequency of abnormal ABI and hypertension than the SVO group. The BAD group had abnormal ABI and hyperlipidemia more frequently than the LAA group. No significant difference was found in diabetes or brachial-ankle pulse wave velocity incidence between the BAD and SVO groups. ABI and vascular risk factors in the BAD group were more similar to those in the LAA group than to those in the SVD group. This finding suggests that pontine lesions extending to the basal pontine surface have an atherosclerotic mechanism in BAD, requiring potent antiplatelet therapy for the secondary prevention of ischemic stroke.

Contrast-enhanced MRI findings of patients with acute Bell palsy within 7 days of symptom onset: A retrospective study.

The brain magnetic resonance imaging (MRI) findings seen in patients with Bell palsy are abnormal contrast enhancement of affected facial nerves. Previous studies were conducted on a few patients, mainly those who had experienced palsy for several weeks. This study investigated the diagnostic usefulness of MRI by examining MRI findings of acute Bell palsy (within 7 days of symptom onset) in a large cohort. Among the patients with Bell palsy (idiopathic unilateral facial palsy) who visited the hospital, 123 patients who underwent contrast-enhanced MRI of the internal auditory canal within 7 days of symptom onset were reviewed retrospectively. MRI examination results were investigated along with the patient's clinical symptoms and electrodiagnostic test results. Based on the MRI results, the frequency of abnormal contrast enhancement and contrast-enhanced areas were investigated. Of the 123 patients, 13 (11%) had normal brain MRI results, and 110 (89%) had abnormal findings. The frequency of abnormal contrast enhancement was not significantly associated with test timing (P = .56). Of the 110 patients with abnormal findings, 65 (59%) showed contrast enhancement in the labyrinthine segment and 36 (33%) in both the labyrinthine segment and geniculate ganglion. Most patients with Bell palsy who are in the acute phase showed abnormal contrast enhancement in their facial nerves, and similar findings were even observed in the examination conducted on the day of symptom onset. Brain MRI helps in the diagnosis of acute Bell palsy.

Cyclophosphamide-containing regimen (TCD) is superior to melphalan-containing regimen (MPT) in elderly multiple myeloma patients with renal impairment.

Renal impairment (RI) is a frequent complication with higher incidence of infections and an important prognostic factor for survival. Melphalan clearance is renal function dependent whereas cyclophosphamide is renal function independent. We investigated which combination regimen should be selected between melphalan-combining regimen (MPT) or cyclophosphamide-combining regimen (TCD) in elderly multiple myeloma (MM) patients with RI. Between 2005 and 2009, 157 newly diagnosed MM patients with RI were included comparing MPT with TCD therapy as initial treatment. Seventy-four patients were given MPT regimen, and 83 patients were given TCD regimen. Baseline characteristics were similar between the MPT and TCD groups. Analysis of different cutoff levels between 25% and 75% quartiles using log-rank test determined that glomerular filtration rate (GFR), 40 ml/min/1.73 m(2) as the cutoff point, yielded the highest difference in event-free survival (EFS) and overall survival (OS). The MPT subgroup with low GFR (GFR <40 ml/min/1.73 m(2)) had poorer response rates than others. The incidence of neutropenia and infection with febrile neutropenia were higher in the MPT subgroup with low GFR than the others (p = 0.016, p < 0.001). Furthermore, mortality due to the infection was higher in the MPT subgroup with low GFR than the others (p < 0.001). EFS was lower in the MPT subgroup with low GFR than the others (p < 0.001). OS was lower in the MPT subgroup with low GFR than the others (p < 0.001). In newly diagnosed elderly MM patients with RI, TCD regimen would be an effective and tolerable treatment option due to the combination of cyclophosphamide independent to renal function and dexamethasone effective for RI.

Primary thyroid marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type: clinical manifestation and outcome of a rare disease - consortium for improving survival of lymphoma study.

PURPOSE: Primary thyroid marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type (pTY-MZL) is an extremely uncommon form of lymphoma. Due to its rarity, the natural history and optimal treatment modality for this disease have yet to be clearly established. METHODS: A total of 27 patients with histologically confirmed pTY-MZL were retrospectively analyzed. RESULTS: The median age of our subjects was 53 years (range 25-82). This study involved 17 females (63.0%) and 10 males (37.0%). Twenty-four out of 27 patients (88.9%) initially presented with localized disease, defined by Ann Arbor stage I/II. Bone marrow involvement was detected in 8.3% of the patients (2 patients), and 91.7% of the patients (25 of 27) were categorized into the low or low-intermediate risk group, according to the International Prognostic Index criteria. Accompanying Hashimoto's thyroiditis was detected in 72% of the patients, whereas thyroglobulin antibody levels were elevated in 70% of the patients. Twenty-six patients were treated with surgery, radiotherapy or chemotherapy, and 25 patients achieved complete remission. During the follow-up period, only 2 patients evidenced progression, and no deaths occurred over the course of the study. CONCLUSION: pTY-MZL tends to be an indolent disease. However, unlike other mucosa-associated lymphoid tissue site MZLs, pTY-MZL was well controlled via several treatment modalities, and the patients' responses were sustained for a prolonged period.

Delayed Rupture of an Anterior Communicating Artery Pseudoaneurysm Caused by Distal Occlusion Thrombectomy Using a Stent Retriever: A Case Report and Mechanism of Injury.

We report a case of delayed rupture of an anterior communicating artery (Acom) pseudoaneurysm following mechanical thrombectomy (MT) of a distal artery occlusion using a stent retriever. An elderly patient with right hemiparesis showed left proximal internal cerebral artery and middle cerebral artery occlusions. During MT, a fragmented thrombus moved to the anterior cerebral artery (ACA). A stent retriever was deployed to the occluded ACA, and the Acom and proximal ACA segment were significantly straightened. Additionally, we attempted a blind exchange mini-pinning (BEMP) technique, but a subarachnoid hemorrhage (SAH) occurred. Bleeding was almost entirely absorbed 9 days after the procedure, but the SAH recurred at 20 days, and computed tomography angiography revealed a new pseudoaneurysm formation in the Acom. We suggest that the proposed mechanism of pseudoaneurysm formation was likely due to the dislocation and avulsion of the Acom perforators when the ipsilateral ACA was pushed and pulled during MT.

The prevalence and clinical characteristics of restless legs syndrome in patients with iron deficiency anemia in Korea.

STUDY OBJECTIVES: While the prevalence and clinical characteristics of restless legs syndrome (RLS) are known to vary according to ethnicity, a detailed evaluation of this condition among patients with iron deficiency anemia (IDA) has not yet been reported in an Asian population. We investigated the prevalence and clinical characteristics of RLS in patients with IDA in Korea compared with age- and sex-matched patients diagnosed with idiopathic RLS. METHODS: This prospective single-center study was performed at a regional university hospital. Consecutive patients with IDA were enrolled over a 4-year period. Clinical interviews and laboratory tests were conducted at the first visit. RLS diagnosis was confirmed through face-to-face interviews. We randomly selected patients with idiopathic RLS without comorbid medical disorders from our sleep center dataset as control patients. The clinical characteristics of both groups were compared. RESULTS: We enrolled 124 patients with IDA. Fifty (40.3%) patients were diagnosed with RLS, with 82% exhibiting severe to very severe symptoms. Patients with IDA and RLS were older and reported more sleep deterioration than patients with IDA without RLS. Patients with IDA and RLS also had a more depressed mood and higher periodic limb movement index scores than patients with idiopathic RLS. CONCLUSIONS: The prevalence of RLS among patients with IDA in Korea was high, with the majority having severe to very severe symptoms. Patients with IDA and RLS had poorer sleep quality and more emotional problems than patients with IDA without RLS. Therefore, patients with IDA should be screened for RLS to prevent adverse effects on the quality of sleep and life.

Bortezomib, thalidomide, dexamethasone induction therapy followed by melphalan, prednisolone, thalidomide consolidation therapy as a first line of treatment for patients with multiple myeloma who are non-transplant candidates: results of the Korean Multiple Myeloma Working Party (KMMWP).

Bortezomib (VELCADE), thalidomide and dexamethasone (VTD), as well as melphalan, prednisolone, and thalidomide (MPT) therapy, are highly effective in patients with multiple myeloma. We evaluated the responses and survival times of 35 patients treated with VTD followed by MPT. All patients were newly diagnosed and non-transplantation candidates. Patients received six cycles of VTD, which were followed by eight cycles of MPT. Approximately 97% of patients exhibited early responses to therapy, as early as the second cycle of VTD. Thirty percent of the responses were high quality, which was defined as a complete response (CR), a near-CR or a very good partial response. High-risk patients were defined as patients with any of the following aberrations: del(13), t(4;14), or del(17p). The remaining patients were defined as standard risk. Eleven high-risk patients showed 100% response rates, including 91% high-quality responses. In contrast, 13 standard-risk patients exhibited 92% response rates, including 61% high-quality responses. The overall 2-year survival rates were 60% in high-risk patients and 85% in standard-risk patients, which was not significantly different. As a first-line therapy, VTD followed by MPT has the potential to provide high-quality responses with durable remission among elderly and high-risk patients (clinicaltrials.gov identifier: NCT00320476).

Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide.

The frequency of thromboembolic events (TE) in Caucasian patients with multiple myeloma (MM) receiving thalidomide as the initial treatment has been reported to be 10~58% without prophylactic anticoagulation. Korean MM patients treated with thalidomide were studied to determine the frequency of TE and associated risk factors. A retrospective medical record review of the Korean MM registry from 25 centers in Korea between 2003 and 2007 was performed. We assessed the incidence of arterial and venous TE and the associated clinical parameters. Three hundred and sixty MM patients (median age 61 years, range 32-88 years) received thalidomide treatment. Fourteen patients (3.9%) developed TE: 12 had venous and two had arterial locations. The sites for the venous TE included lungs (seven), lower extremities (four), upper extremities (one), and neck (one). Arterial TE developed in cerebral and peripheral arteries each. No single clinical parameter such as prerequisite for the metabolic syndrome, disease status, and treatment regimen were predictive for the development of TE. The frequency of TE in patients who received thalidomide as initial therapy (7/155) was not different from those who received thalidomide for progressive or relapsed disease (7/205, p = 0.592). The frequency of TE during thalidomide treatment in Korean patients with MM was low. No significant clinical factor was found to be a risk factor. The subgroup requiring thromboprophylaxis among the Korean patients with MM, receiving thalidomide, needs to be clarified.

Anti­survival and pro­apoptotic effects of meridianin C derivatives on MV4­11 human acute myeloid leukemia cells.

Meridianin C is a marine natural product with anticancer activity. Several meridianin C derivatives (compounds 7a­j) were recently synthesized, and their inhibitory effects on pro­viral integration site for Moloney murine leukemia virus (PIM) kinases, as well as their antiproliferative effects on human leukemia cells, were reported. However, the anti­leukemic effects and mechanisms of action of meridianin C and its derivatives remain largely unknown. The aim of the present study was to investigate the effects of meridianin C and its derivatives on MV4­11 human acute myeloid leukemia cell growth. The parent compound meridianin C did not markedly affect the viability and survival of MV4­11 cells. By contrast, MV4­11 cell viability and survival were reduced by meridianin C derivatives, with compound 7a achieving the most prominent reduction. Compound 7a notably inhibited the expression and activity of PIM kinases, as evidenced by reduced B­cell lymphoma­2 (Bcl­2)­associated death promoter phosphorylation at Ser112. However, meridianin C also suppressed PIM kinase expression and activity, and the pan­PIM kinase inhibitor AZD1208 only slightly suppressed the survival of MV4­11 cells. Thus, the anti­survival effect of compound 7a on MV4­11 cells was unrelated to PIM kinase inhibition. Moreover, compound 7a induced apoptosis, caspase­9 and ­3 activation and poly(ADP­ribose) polymerase (PARP) cleavage, but did not affect death receptor (DR)­4 or DR­5 expression in MV4­11 cells. Compound 7a also induced the generation of cleaved Bcl­2, and the downregulation of myeloid cell leukemia (Mcl)­1 and X­linked inhibitor of apoptosis (XIAP) in MV4­11 cells. Furthermore, compound 7a increased eukaryotic initiation factor (eIF)­2α phosphorylation and decreased S6 phosphorylation, whereas GRP­78 expression was unaffected. Importantly, treatment with a pan­caspase inhibitor (z­VAD­fmk) significantly attenuated compound 7a­induced apoptosis, caspase­9 and ­3 activation, PARP cleavage, generation of cleaved Bcl­2 and downregulation of Mcl­1 and XIAP in MV4­11 cells. Collectively, these findings demonstrated the strong anti­survival and pro­apoptotic effects of compound 7a on MV4­11 cells through regulation of caspase­9 and ­3, Bcl­2, Mcl­1, XIAP, eIF­2α and S6 molecules.

Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma.

BACKGROUND: Bortezomib has significantly advanced the treatment of patients with multiple myeloma (MM). However, considering that most patients with MM are elderly, bortezomib-related morbidity should be thoroughly studied to ensure the safe use of this drug. Herpes zoster has been reported as a possible adverse event associated with bortezomib because a major target of bortezomib, nuclear factor-kappaB, is known to be involved with T-cell immunity. PATIENTS AND METHODS: We performed a retrospective analysis of the incidence of herpes zoster among 282 patients treated with a bortezomib-containing regimen. RESULTS: During the patients' pre-bortezomib treatment (median, 2.14 years), the incidence of herpes zoster was 11% (31 of 282 patients). However, after the patients were treated with bortezomib, the incidence increased to 22.3% (63 of 282 patients), of which almost all occurrences were within the first 3 cycles (median duration, 41 days). The time interval from diagnosis to bortezomib initiation date was shorter in herpes zoster-positive patients than in herpes zoster-negative patients (2.14 +/- 1.87 years vs. 3.38 +/- 2.95 years; P = .002). Disease duration, previous herpes zoster infection, disease stage and type of myeloma, and the type and intensity of previous treatments failed to show any relationship with herpes zoster. These findings suggest that longer history of disease and treatments did not affect the occurrence of herpes zoster, nor did the type of bortezomib regimens or their toxicities. CONCLUSION: Bortezomib can increase the incidence of herpes zoster regardless of disease duration, previous treatments, and concomitantly administered drugs. Thus, the occurrence of herpes zoster should be monitored during bortezomib treatment.

Induction chemotherapy followed by up-front autologous stem cell transplantation may have a survival benefit in high-risk diffuse large B-cell lymphoma patients.

We compared the outcomes of patients with higher-risk diffuse large B-cell lymphoma (DLBCL) who were treated with either up-front autologous stem cell transplantation (ASCT) or salvage chemotherapy followed by delayed ASCT after relapse. Data for 122 DLBCL patients who underwent ASCT as up-front or salvage treatment were analyzed. The 3-year overall survival (OS) rate in DLBCL patients who underwent up-front ASCT was 76.6%, and the rate for those who underwent delayed ASCT was 60.9% (p = 0.017). In a subgroup analysis of patients with a high-intermediate/high-risk age-adjusted International Prognostic Index, achievement of complete remission translated into improved OS in the up-front ASCT group, whereas patients who achieved partial remission had similar OS rates in both groups. The up-front ASCT group had improved OS in patients aged <50 years or with good performance status, whereas the OS rates of both groups were similar in patients aged ≥ 60 years or with poor performance status. When the OS outcome is analyzed by the number of factors (no complete remission during R-CHOP induction chemotherapy, age ≥ 50 years, and performance status ≥ 2), the 3-year OS rates of patients with zero or one, two, and three clinical factors were 80.2%, 51.6%, and 0%, respectively (p < 0.001). In conclusion, in higher-risk DLBCL patients, induction chemotherapy followed by up-front ASCT may have a survival benefit compared with induction chemotherapy alone in highly selected patients who have achieved a complete remission, who are aged <50 years, and who have a good performance status at diagnosis.

Chronic kidney disease and intravenous thrombolysis in acute stroke: A systematic review and meta-analysis.

BACKGROUND: The association between chronic kidney disease (CKD) and hemorrhagic complications or clinical outcomes in patients treated with intravenous (IV) thrombolytic agents is controversial. METHODS: We searched multiple databases for studies on the association between CKD and symptomatic intracerebral hemorrhage (ICH) and/or clinical outcomes in acute stroke patients treated with IV tissue plasminogen activator (tPA). Observational studies that evaluated the association between CKD and outcomes after adjusting for other confounding factors were eligible. We assessed study quality and performed a meta-analysis. The main outcome was symptomatic ICH. The secondary outcomes were poor functional status at 3 months using the modified Rankin Scale, mortality at 3 months, and any ICH. RESULTS: Seven studies were selected based on our eligibility criteria. Of 7168 patients treated with IV tPA, 2001 (27.9%) had CKD. Patients with CKD had a higher risk of symptomatic ICH and mortality [pooled odds ratio (OR) 1.56, 95% confidence interval (CI) 1.05-2.33 and pooled OR 1.70, 95% CI 1.03-2.81, respectively]. Patients with CKD were likely to have an increased risk of poor outcome at 3 months. There was no significant association between CKD and any ICH. CONCLUSIONS: Chronic kidney disease may significantly affect symptomatic hemorrhagic complications and poor clinical outcomes following administration of IV tPA.

Effects of polychlorinated biphenyls on the development of neuronal cells in growth period; structure-activity relationship.

Polychlorinated biphenyls (PCBs) are accumulated in our body through food chain and cause a variety of adverse health effects including neurotoxicities such as cognitive deficits and motor dysfunction. In particular, neonates are considered as a high risk group for the neurotoxicity of PCBs exposure. The present study attempted to analyze the structure-activity relationship among PCB congeners and the mechanism of PCBs-induced neurotoxicity. We measured total protein kinase C (PKC) activities, PKC isoforms, reactive oxygen species (ROS), and induction of neurogranin (RC-3) and growth associated protein-43 (GAP-43) mRNA in cerebellar granule cells of neonatal rats with phorbol 12, 13-dibutyrate ([(3)H]PDBu) binding assay, western blot, ROS assay, and reverse transcription PCR (RT-PCR) analysis respectively following the different structural PCBs exposure. Only non-coplanar PCBs showed a significant increase of total PKC-α and ßII activity as measured with [(3)H]PDBu binding assay. ROS were more increased with non-coplanar PCBs than coplanar PCBs. The mRNA levels of RC-3 and GAP-43 were more induced with non-coplanar PCBs than coplanar PCBs, indicating that these factors may be useful biomarkers for differentiating non-coplanar PCBs from coplanar PCBs. Non-coplanar PCBs may be more potent neurotoxic congeners than coplanar PCBs. This study provides evidences that non-coplanar PCBs, which have been neglected in the risk assessment processes, should be added in the future to improve the quality and accuracy of risk assessment on the neuroendocrinal adverse effects of PCBs exposures.

Waldeyer's ring marginal zone B cell lymphoma: are the clinical and prognostic features nodal or extranodal? A study by the Consortium for Improving Survival of Lymphoma (CISL).

There has been controversy surrounding Waldeyer's ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4 %). Ann Arbor stage III/VI disease was present in 48.1 % (25 of 52). The response rate of the 27 stage I/II patients was 88.9 %, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7 years (95 % CI 2.5-4.9 years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5 %, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P < 0.001).