Characteristics of Month-by-Month Blood Pressure Variability in Patients on Hemodialysis.

INTRODUCTION: Poor prognosis in hemodialysis (HD) patients is due to the increased prevalence of cardiovascular diseases among them. We previously reported that higher visit-by-visit blood pressure variability is associated with increased cardiovascular mortality in HD patients. This present study aimed to investigate the characteristics of month-by-month blood pressure variability (MMBPV) in these patients. METHODS: A total of 324 maintenance HD patients, who could be followed up for 60 months, were recruited. We used standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM) in pre- and post-dialysis systolic blood pressure (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) as an index of MMBPV. We investigated (1) the reproducibility of MMBPV, (2) relationship between these values and background factors, and (3) association between these values and mortality. RESULTS: MMBPV (pre- and post-SD, pre- and post-CV, and pre- and post-VIM) showed significant reproducibility (intraclass correlation, 0.483 [p < 0.001], 0.553 [p < 0.001], 0.450 [p < 0.001], 0.518 [p < 0.001], 0.456 [p < 0.001], and 0.522 [p < 0.001], respectively). High pre-VIM was associated with high interdialytic weight gain and poor nutritional status. High post-VIM was associated with glucose intolerance, high interdialytic weight gain, and poor nutritional status and associated with high rate of cardiovascular deaths independent of other factors (hazard ratio: 1.104, 95% confidence interval: 1.011-1.207, p = 0.028). CONCLUSION: These data suggested that pre- and post-VIM in HD patients are reproducible and associated with various background factors, and especially post-VIM is independently correlated with cardiovascular mortality. Further studies are necessary to confirm the mechanism of increased post-VIM and clarify whether reducing post-VIM can improve the prognosis of HD patients.

Cerebral foreign body granulomas after mechanical thrombectomy: Two case reports and a review of the literature.

OBJECTIVES: A foreign body granuloma after an endovascular intervention is a rare complication. Some cases of foreign body granulomas, especially after coil embolization, have been reported. However, only four cases of foreign body granulomas after mechanical thrombectomy (MT) have previously been reported. The current study reports two cases of post-MT foreign body granulomas, including a biopsy-proven case. MATERIAL AND METHODS: Case 1: A 73-year-old woman presented with complete occlusion of the right middle cerebral artery. Cerebral angiography and MT were successfully performed with improvement in clinical symptoms. Left hemiparesis and a disturbance in attention appeared after discharge and progressed slowly. She was re-admitted to our hospital 120 days after cerebral infarction owing to foreign body granulomas diagnosed on biopsy. Case 2: A 78-year-old man presented with occlusion of the left cervical internal carotid artery and the left middle cerebral artery. Cerebral angiography, percutaneous transluminal angioplasty, and MT were successfully performed. On the 34th day, he experienced progressive consciousness disorder because of foreign body granulomas. Both cases were successfully treated with steroid therapy. RESULTS: MRI after steroid treatment showed the disappearance of most nodular lesions and improvement of the encephalopathy. CONCLUSIONS: The cause of the granuloma may be an allergic reaction to the hydrophilic polymers that peel from endovascular devices. Steroid therapy is an effective treatment; therefore, neurologists should consider this complication when neurological symptoms or signs on image appears or worsens. A reliable diagnosis is important for prompt treatment.

Amount and selectivity of proteinuria may predict the treatment response in post-transplant recurrence of focal segmental glomerulosclerosis: a single-center retrospective study.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. To date, few studies have investigated predictive factors for treatment responses in recurrent FSGS. METHODS: We retrospectively analyzed 16 patients who were < 16 years at the age of onset and had post-transplant recurrence of FSGS from 1993 to 2018. Patients who achieved complete remission or partial remission after initiating therapy for recurrent FSGS were defined as responders. We compared several clinical characteristics between responders and non-responders. Time to remission was also analyzed. RESULTS: Ten patients were responders, and six patients were non-responders. Univariate analysis showed that responders had a significantly lower amount of maximum proteinuria at the time of recurrence (P = 0.015) and more highly selective proteinuria (P = 0.013) than non-responders. The time to remission from initiation of therapy was 2 months (interquartile range 0.2-4.4). In all responders, except for one patient, remission was achieved within 6 months. CONCLUSIONS: Therapeutic responses may be predicted by examining the amount and selectivity of proteinuria at the time of recurrence. Further studies with larger numbers of patients are clearly required to validate these findings.

[Anterior Interosseous Nerve Palsy with Isolated Flexion Palsy of the Thumb or Index Finger as an Initial Symptom:Two Case Reports].

Case 1: A 73-year-old man who had undergone neurolysis for right cubital tunnel syndrome complained of difficulty using chopsticks. Froment's sign test showed that the interphalangeal(IP)joint of the right thumb that had flexed preoperatively was extended. This finding was considered to indicate recovery from ulnar neuropathy, and the patient was closely followed up. One year later, the patient was unable to push a camera shutter button and was unable to flex the IP joint of the thumb and the distal interphalangeal(DIP)joint of the index finger, a characteristic symptom of anterior interosseous nerve(AIN)palsy. Therefore, the patient underwent AIN neurolysis and subsequently reported slight improvement in his condition. Case 2: A 60-year-old woman reported difficulty performing computer mouse clicks with her right hand. As flexing the index finger DIP joint was difficult, a local lesion was suspected, and the patient was closely followed up. One year later, the patient was unable to push the button of a ballpoint pen with her thumb. Extension of the thumb and index finger indicated AIN palsy. The patient refused treatment and was only followed up. The following year, the patient reported that the weakness improved. Simultaneous flexion palsy of the thumb and index finger can lead to a diagnosis of AIN palsy. However, flexion palsy of a single finger in incomplete AIN palsy, as reported here, is often overlooked because of its similarity to the flexor tendon rupture. Awareness regarding this incomplete form of AIN palsy is needed for early and correct diagnosis.

Prevalence of Microembolic Signals in Embolic Stroke of Undetermined Source and Other Subtypes of Ischemic Stroke.

Background and Purpose- Embolic stroke of undetermined source (ESUS) has been proposed to cause thromboembolic infarction from unknown but potential embolic sources. However, an embolus remains undetected in ESUS. The goal of this study was to characterize the prevalence and risk factors of microembolic signals (MESs) in ESUS. Methods- We examined 108 patients with acute ischemic stroke in the internal carotid artery territory or transient ischemic attack within 14 days of symptom onset and who were admitted to our hospital between April 2017 and March 2019. MESs were monitored in the middle cerebral artery on transcranial Doppler for 60 minutes. We examined the prevalence and number of MES in ESUS and other stroke subtypes, such as cardioembolism, large artery atherosclerosis, cerebral small vessel disease, and transient ischemic attack. The present study was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000031913). Results- MESs were detected in 33 (31%) of 108 patients. ESUS showed the highest proportion (12/24 [50%]), followed by large artery atherosclerosis (8/20 [40%]), cardioembolism (6/18 [33%]), transient ischemic attack (4/24 [17%]), and cerebral small vessel disease (3/21 [14%]). Univariate analysis showed that higher systolic blood pressure, body mass index, hemoglobin A1c, and ESUS were significantly associated with MES. In multiple logistic regression analysis, ESUS remained significantly associated with MES after adjustment for described covariates from univariate analysis (odds ratio, 2.86 [95% CI, 1.01-8.08]). Conclusions- This study demonstrated significant association of ESUS with MES, supporting the embolic nature of this stroke subtype. Registration- URL: https://upload.umin.ac.jp. Unique identifier: UMIN000031913.

[Lymphorrhea at the Site of Repeated Fascia Lata Harvesting:A Case Report].

This 74-year-old man had undergone a third re-operation for anaplastic meningioma in the convexity six weeks before he was referred to us. He presented with a bulge on the lateral aspect of the left thigh. We observed a fresh fascia lata harvesting scar that extended peripherally from an old proximal scar. The bulge was colorless. The aspirated subcutaneous fluid(more than 200mL)was watery and yellowish;there was no evidence of abscess or hematoma. Although the bulge shrank after aspiration and the placement of a compression bandage, it recurred in three days. Surgery-associated lymphorrhea was the diagnosis given. Goreisan, a herbal medicine for hydrostatic modulation, was administered. One week later, the bulge diminished in size. Harvesting of the fascia lata in the lateral aspect of the thigh is usually safe. However, additional dissection and peripheral extension due to repeated harvesting risks damaging the superficial lymphatic pathways because of scar formation after earlier surgeries and the hyperdense distribution of the lymphatic pathways in the peripheral part. When subcutaneous fluid collection after fascia lata harvesting is refractory, lymphorrhea must be considered in the differential diagnosis.

PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression in pulmonary emphysema and chronic obstructive pulmonary disease with resected lung squamous cell carcinoma.

BACKGROUND: Emphysema and chronic obstructive pulmonary disease (COPD) are well known independent risk factors for lung cancer. However, the developmental mechanisms between emphysema/COPD and lung cancer remain unknown. The purpose of this study was to evaluate PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression in squamous cell carcinoma (SCC) associated with emphysema/COPD. METHODS: A total of 59 patients with squamous cell lung carcinoma (SCC) resected between 2008 and 2012 were retrospectively reviewed. Emphysema was assessed according to the Goddard score. Total severity was divided into none-mild (0-7), moderate (8-15), and severe (≥ 16). Local severity around the existing tumor was divided into no emphysema (0) and presence of emphysema (1-4). COPD severity was based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression were evaluated by immunohistochemistry (IHC). Expression level was classified as tumor cells (TC) 3 (≥ 50%), TC2 (5-49%), TC1 (1-4%), or TC0 (< 1%), and as tumor-infiltrating immune cells (IC) 3 (≥ 50%), IC2 (5-49%), IC1 (1-4%), or IC0 (< 1%) for PD-L1. Expression level was compared between none-mild/moderate-severe total emphysema, no/presence of local emphysema, no COPD/COPD, and GOLD 1/GOLD 2, 3. RESULTS: PD-L1 expression was significantly correlated with severity of emphysema in TC0, 1, 2 vs. TC3 (P = 0.012). PD-L1 was significantly higher inversely in none-mild emphysema compared to moderate-severe (95% CI, 0.061-5.852, P = 0.045). There were no other significant associations between PD-L1, FGFR1, PIK3CA, PTEN, and p16 expression and total/local severity of emphysema or presence of COPD/GOLD stage. CONCLUSIONS: PD-L1 expression in SCC was correlated with severity of emphysema in TC0, 1, 2 vs. TC3 and more frequent in none-mild emphysema than moderate-severe emphysema.

Idiopathic spinal cord herniation: consideration of its pathogenesis based on the histopathology of the dura mater.

INTRODUCTION: We present a patient with idiopathic spinal cord herniation (ISCH) whose dura mater was histopathologically examined to elucidate its pathogenesis. CASE REPORT: A 33-year-old previously healthy man presented with progressive walking difficulty, spasticity of the right lower leg, and hyperesthesia below the right chest. Neuroimaging revealed right ventral displacement of the spinal cord at T5-6. The diagnosis was ISCH and he underwent release of the herniation from the ventral dural opening. Dural biopsy at the edge of the ventral opening and in the dorsal durotomy was performed. Postoperatively, his gait was improved. Histopathological examination of the ventral dural specimen showed non-specific degeneration, i.e., loose arrangements of collagen fibers, edematous changes, minor inflammatory cell infiltration, and angiogenesis. The specimen from the dorsal durotomy was normal. CONCLUSION: It is unclear whether the observed degeneration besides the ventral opening was the primary cause of ISCH or reflected secondary changes resulting from cumulative damage due to pulsation of the herniated spinal cord. However, the degeneration limited to the ventral opening suggests that ISCH was a local event in an individual with a normal dural theca.

Risk factors for hyponatremia after hypotonic fluid infusion.

BACKGROUND: Hypotonic maintenance i.v. fluids (IVF) pose a higher risk of hyponatremia than isotonic maintenance IVF, but isotonic maintenance IVF can result in excess sodium (Na) load in children. This study analyzed the incidence and risk factors for hyponatremia in children given hypotonic fluids with different Na concentrations and different maintenance rates. METHODS: We performed a retrospective analysis using medical charts of children aged 3 months-15 years. The children were normonatremic (Na ≥135 mmol/L and <145 mmol/L) before IVF, and given IVF containing 35 mmol/L Na at a 100% maintenance rate (Na 35) or fluids containing 84 mmol/L Na at a 70% maintenance rate (Na 84) for 24-48 h. RESULTS: Of a total of 463 children, hyponatremia (Na <135 mmol/L) occurred in 46/275 children (17%) given Na 35, and 16/188 (9%) given Na 84 (P = 0.01). On multivariate logistic regression analysis, Na 35 (OR, 2.19; 95%CI: 1.04-4.62), low clinical dehydration scale (CDS) score before IVF (OR, 0.17; 95%CI: 0.06-0.49), and high body temperature 24-48 h after maintenance IVF (OR, 2.39; 95%CI: 1.79-3.18) were independent risk factors for hyponatremia. CONCLUSIONS: Maintenance IVF with low Na concentration at a 100% maintenance rate, low CDS before IVF, and a high body temperature 24-48 h after maintenance IVF are independent risk factors for hyponatremia.

[False Aneurysm Formation at the Origin of the M2 Segment of the Middle Cerebral Artery Following a Blunt Head Trauma:A Case Report].

A 43-year-old man fell from a 1m-high truck loading platform and sustained an injury in the occiput. On admission, he was alert and neurologically intact. Computed tomography(CT)showed hemorrhage in the right sylvian fissure and parenchyma adjacent to the sphenoid wing. Magnetic resonance angiography detected no abnormalities. The course was uneventful for 11 days. However, on the 12th day, he spontaneously manifested with stupor. CT and CT angiography revealed expansion of the hemorrhage and an aneurysm arising from the origin of the M2 segment of the right middle cerebral artery. After superficial temporal artery to middle cerebral artery bypass, the aneurysm, a reddish pulsatile mass, was removed from the origin of the torn M2 segment, and the laceration was sutured. The histological diagnosis was false aneurysm. He recovered and was discharged 4 months after the trauma. Traumatic cerebral aneurysms are rare in the proximal segment of the middle cerebral artery. However, they should be distinguished from nontraumatic true aneurysms in the same region and treated as false aneurysms, which are major and critical traumatic aneurysms, for favorable outcomes.

CSF and clinical data are useful in differentiating CNS inflammatory demyelinating disease from CNS lymphoma.

BACKGROUND: It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma. OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma. METHODS: We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma ( n = 12), or glioma ( n = 10). We detected diagnostic markers using logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: Median CSF IL-10 and sIL-2R levels were higher in CNS lymphoma patients than in MS, NMOSD, or TDL patients. Logistic regression revealed that CSF sIL-2R levels predicted CNS lymphoma. In the ROC analysis of CSF sIL-2R levels, the area under the curve was 0.867, and the sensitivity and specificity were 83.3% and 90.0%, respectively. CONCLUSION: CSF sIL-2R levels can be used to differentiate CNS lymphoma from CNS IDDs. Further studies may identify other applications of CSF as a diagnostic biomarker.

Prognostic value of the Glasgow Prognostic Score for patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy.

BACKGROUND: The aim of the present study was to evaluate the prognostic significance of the Glasgow Prognostic Score (GPS) in metastatic renal cell carcinoma (mRCC) patients treated by cytoreductive nephrectomy (CN), and the accuracy of the GPS as a prognostic factor. METHODS: We retrospectively analyzed the data of patients who underwent CN for mRCC between March 1984 and August 2015. In accordance with the GPS criteria, the patients were classified into three groups: GPS 0: C-reactive protein (CRP) ≤ 1.0 mg/dl and albumin ≥ 3.5 g/dl; GPS 1: CRP > 1.0 mg/dl or albumin < 3.5 g/dl; and GPS 2: CRP > 1.0 mg/dl and albumin < 3.5 g/dl. RESULTS: We enrolled 170 patients (72% male; median age 63.5 years). Fifty-six (33%), 67 (39%), and 47 (28%) patients had a GPS of 0, 1, and 2, respectively. The median overall survivals after CN were 52.4, 19.1, and 8.9 months for patients with a GPS of 0, 1, and 2, respectively (P < 0.0001). In addition to the GPS, Eastern Cooperative Oncology Group performance status (ECOG-PS), Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification, histology, sarcomatoid change, clinical T stage, primary tumor size, number of metastatic organs, non-regional lymph node metastasis, and liver metastasis were included in the Cox hazards regression model. Multivariate analysis of these factors revealed that the GPS was an independent prognostic factor of overall survival (P < 0.0001). Harrell's concordance index in the multivariate prognostic model based on ECOG-PS, MSKCC risk criteria, histology, sarcomatoid change, clinical T stage, primary tumor size, number of metastatic organs, non-regional lymph node metastasis, and liver metastasis was 0.609, which increased to 0.652 after the inclusion of the GPS. CONCLUSIONS: GPS represents an independent prognostic factor for patients who undergo CN for mRCC.

Remote Limb Ischemic Conditioning during Cerebral Ischemia Reduces Infarct Size through Enhanced Collateral Circulation in Murine Focal Cerebral Ischemia.

BACKGROUND: Remote ischemic conditioning (RIC) induces protection in focal cerebral ischemia. The conditioning is divided into pre-, per-, and postconditioning. However, the mechanisms of RIC remain unknown. OBJECTIVES: This study aimed to determine the most effective subtype of RIC. We also examined involvement of collateral circulation on RIC. METHODS: Transient middle cerebral artery occlusion (MCAO) was performed with nylon sutures in adult C57BL/6 mice under the monitoring of cerebral blood flow (CBF). Fifty mice were divided into 5 groups: MCAO control group, delayed pre-RIC group (RIC 24 hours before MCAO), early pre-RIC group (RIC 5 minutes before MCAO), per-RIC group (RIC during MCAO), and post-RIC group (RIC 5 minutes after MCAO). In other middle cerebral artery (MCA) control and per-RIC groups, collateral circulation was visualized with latex compound perfusion. RESULTS: After MCAO, CBF was reduced by 80% in all groups. At the end of MCAO, relative increase in CBF in per-RIC group was significantly greater than that in MCA control, whereas the infarct volume in per-RIC group was significantly smaller than that in other groups. The diameter of leptomeningeal anastomosis was larger in the per-RIC group than that in the control group. CONCLUSIONS: Among the 4 RIC procedures, only the per-RIC group showed clear brain protection. Enhancement of collateral circulation could play a role in the protective effect of per-RIC.

[Formation of a Subcutaneous Amputation Neuroma after Incomplete Endoscopic Carpal Tunnel Release Resulting in Complex Regional Pain Syndrome:A Case Report].

This 64-year-old woman had undergone endoscopic carpal tunnel release(ECTR)for right carpal tunnel syndrome 16 months earlier. Thereafter, she reported persistent dysesthesia in the thumb and index finger, developed burning pain in the middle and ring finger, paleness, coldness, and edema of the hand, a decreased range in hand motion, and a painful subcutaneous nodule just distal to the portal in the forearm. Based on physical, radiological, and electrophysiological studies, the diagnosis was incomplete carpal tunnel release associated with complex regional pain syndrome(CRPS). At open revision surgery, the carpal tunnel was released completely and the nodule was removed. Symptoms other than hypesthesia in the middle and ring fingers improved. Pathologically, the nodule was an amputation neuroma. Her CRPS was attributed to ECTR complications; i.e., persistence of median nerve compression and the formation of an amputation neuroma in the palmar cutaneous branch of the ulnar nerve at the portal. Surgeons must be aware that ECTR, a less invasive technique, may result in serious complications including CRPS.

Expression of enhancer of zeste homolog 2 correlates with survival outcome in patients with metastatic breast cancer: exploratory study using primary and paired metastatic lesions.

BACKGROUND: In metastatic breast cancer, the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as the Ki-67 index sometimes change between primary and metastatic lesions. However, the change in expression levels of enhancer of zeste homolog 2 (EZH2) between primary and metastatic lesions has not been determined in metastatic breast cancer. METHODS: Ninety-six metastatic breast cancer patients had biopsies or resections of metastatic lesions between September 1990 and February 2014 at the Kanagawa Cancer Center. We evaluated ER, PR, HER2, Ki-67, and EZH2 in primary lesions and their corresponding metastatic lesions using immunohistochemistry. We examined the change in expression of EZH2 between primary and metastatic lesions, the correlation between the expression of EZH2 and the expression of other biomarkers, and the relationship between EZH2 expression and patient outcome in metastatic breast cancer. RESULTS: EZH2 expression was significantly higher in metastatic lesions compared with primary lesions. EZH2 expression was highly correlated with Ki-67 expression in primary and metastatic lesions. High-level expression of EZH2 was associated with poorer disease-free survival (DFS) outcomes in patients with primary lesions (P < 0.001); however, high-level expression of EZH2 was not associated with poorer DFS outcomes in patients with metastatic lesions (P = 0.063). High-level expression of EZH2 was associated with poorer overall survival (OS) postoperatively in patients with primary (P = 0.001) or metastatic lesions (P = 0.005). High-level expression of EZH2 was associated with poorer OS outcomes after recurrence in patients with metastatic lesions (P = 0.014); however, high-level expression of EZH2 was not associated with poorer OS outcomes after recurrence in patients with primary lesions (P = 0.096). High-level expression of EZH2 in metastatic lesions was independently associated with poorer OS outcomes after recurrence. CONCLUSIONS: EZH2 expression was significantly increased in metastatic lesions compared with primary lesions. High-level expression of EZH2 in metastatic lesions was associated with poorer OS outcomes after primary surgery and recurrence.

Genetic Counseling for Couples Seeking Noninvasive Prenatal Testing in Japan: Experiences of Pregnant Women and their Partners.

The recent advent of noninvasive prenatal testing (NIPT) has had a significant impact in the field of prenatal testing. Although reports on pregnant women who used NIPT have accumulated, little is known about the experiences of their male partners. In this study, we assessed the experiences of couples who were expecting a child and undergoing NIPT, with a focus on both the pregnant women and their partners. Questionnaires were administered to 282 participants focusing on their specific experiences at three time points: after pre-test counseling (first visit), when undergoing NIPT (second visit), and when results were received (third visit). Responses were analyzed to assess the differences between pregnant women and their partners. We found that more partners selected "family" as their first information source about NIPT and "my partner" as the first person to request NIPT than did pregnant women (35.6 vs. 5.9 %; p < 0.001 and 19.3 vs.1.5 %; p < 0.001). However, pregnant women more often consulted others including family and friends until undergoing NIPT than their partners (89.1 vs. 54.6 %; p < 0.001). Our findings suggest that it is important to encourage male partners to be actively involved in the NIPT decision-making process. Differences between pregnant women and their partners should be seriously considered when providing genetic counseling.

[Efficacy and Safety of Lenvatinib for Unresectable Anaplastic Thyroid Cancer].

The 208 trial showed that lenvatinib has a significant antitumor effect on unresectable anaplastic thyroid cancer(ATC). Herein, we present a retrospective review of data from 7 patients with unresectable ATC who received lenvatinib in our hospital between May 2015 and October 2016. Two patients were men and 5 were women. The median age was 78(range, 72-85)years, and 1 patient had Stage IV A disease, 1 had Stage IV B, and 5 had Stage IV C at diagnosis, respectively. Three patients experienced a partial response and 1 patient experienced stable disease. The response rate was 43%, and the disease control rate was 57%. The median progression-free survival(PFS)was 4.1(range, 1.1-12.2)months. Grade 3 and Grade 4 gastrointestinal hemorrhage were observed in 2patients and Grade 3 anorexia was observed in 1 patient. Further clinical research seems to be needed to establish a treatment strategy involving lenvatinib for ATC.

Pregnancy-related relapse risk factors in women with anti-AQP4 antibody positivity and neuromyelitis optica spectrum disorder.

BACKGROUND: Few reports describe the influence pregnancy has on the annualized relapse rate (ARR) in neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To examine pregnancy-related attacks (attacks during pregnancy or within 1 year postpartum) and identify the risk factors for an attack in Japanese NMOSD patients. METHODS: We retrospectively reviewed 139 Japanese women whom had aquaporin-4 (AQP4) antibody-positive NMOSD. Among the 114 patients with information, 47 women had 56 pregnancies. We compared the ARR before, during and after pregnancy. RESULTS: Of the 47 NMOSD patients with pregnancy, 22 women (46.8%) had a pregnancy-related attack of the disease (either an onset event or a relapse). The ARR was significantly higher in the first 3 months postpartum (1.80 ± 2.04), than before the pregnancy (0.57 ± 1.16; p = 0.0043) and did not significantly decrease during pregnancy. The ARR before hospitalization and treatment was analyzable in 55 patients without pregnancy and was 1.09 ± 1.17. Among the 11 patients with onset before pregnancy, nine patients had a pregnancy-related attack with a relapse in the previous year, and their immunosuppression was discontinued or made to be at low doses; while the two patients on higher-dose therapies were relapse-free. CONCLUSION: In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.

Silent Cerebral Ischemic Lesions After Catheter Ablation of Atrial Fibrillation in Patients on 5 Types of Periprocedural Oral Anticoagulation　- Predictors of Diffusion-Weighted Imaging-Positive Lesions and Follow-up Magnetic Resonance Imaging.

BACKGROUND: The aim of this study was to identify the predictors of silent cerebral ischemic lesions (SCIL) after catheter ablation of atrial fibrillation (AF) and to determine whether SCIL develop into cerebral infarcts in patients with 5 types of oral anticoagulants (OAC). METHODS AND RESULTS: We retrospectively studied 286 consecutive patients (median, 67 years; 208 male; paroxysmal/persistent/long-standing persistent AF [LSP-AF], 147/90/49) who received periprocedural OAC and underwent MRI after the procedure. Warfarin (n=46) was continued, while dabigatran (n=47), rivaroxaban (n=89), apixaban (n=87), and edoxaban (n=17) were discontinued on the day of the procedure. I.v. heparin was infused to maintain an activated clotting time of 300-350 s during the procedure. Fifty-eight SCIL in 40 patients (14.0%) were identified on diffusion-weighted MRI. On multivariate logistic analysis, LSP-AF and dabigatran use were significant positive predictors of SCIL (OR, 2.912 and 2.287; P=0.006 and 0.042, respectively). Among 34 patients with 49 SCIL undergoing follow-up MRI, 45 (91.8%) of the lesions disappeared and 4 lesions developed into chronic cerebral infarcts. The SCIL with development into infarcts had a larger lesion diameter than those without (median, 6.55 mm vs. 4.2 mm; P=0.002). CONCLUSIONS: LSP-AF and dabigatran use were independent risk factors for post-ablation SCIL in patients with uninterrupted warfarin and interrupted non-vitamin K antagonist OAC, but the majority of SCIL disappeared.

Bacterial Long-Chain Polyunsaturated Fatty Acids: Their Biosynthetic Genes, Functions, and Practical Use.

The nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. These LC-PUFAs are physiologically important compounds in bacteria and eukaryotes. Although little is known about the biosynthetic mechanisms and functions of LC-PUFAs in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to LC-PUFA-producing bacteria and some eukaryotes have revealed the notably diverse organization of the pfa genes encoding a polyunsaturated fatty acid synthase complex (PUFA synthase), the LC-PUFA biosynthetic processes, and tertiary structures of the domains of this enzyme. In bacteria, LC-PUFAs appear to take part in specific functions facilitating individual membrane proteins rather than in the adjustment of the physical fluidity of the whole cell membrane. Very long chain polyunsaturated hydrocarbons (LC-HCs) such as hentriacontanonaene are considered to be closely related to LC-PUFAs in their biosynthesis and function. The possible role of LC-HCs in strictly anaerobic bacteria under aerobic and anaerobic environments and the evolutionary relationships of anaerobic and aerobic bacteria carrying pfa-like genes are also discussed.