Successful treatment with atezolizumab combination chemotherapy in a patient with high-grade fetal adenocarcinoma of the lung: A case report.

High-grade fetal lung adenocarcinoma (H-FLAC) is a rare tumor, with little known of its response to chemotherapy with or without an immune checkpoint inhibitor or of its molecular profile. We report the first case of a 56-year-old man with stage IV H-FLAC who was successfully treated with carboplatin plus nab-paclitaxel in combination with atezolizumab. In addition, the tumor was found to be positive for amplification of the human epidermal growth factor receptor 2 gene.

Predicting cerebral infarction in patients with atrial fibrillation using machine learning: The Fushimi AF registry.

The CHADS2 and CHA2DS2-VASc scores are widely used to assess ischemic risk in the patients with atrial fibrillation (AF). However, the discrimination performance of these scores is limited. Using the data from a community-based prospective cohort study, we sought to construct a machine learning-based prediction model for cerebral infarction in patients with AF, and to compare its performance with the existing scores. All consecutive patients with AF treated at 81 study institutions from March 2011 to May 2017 were enrolled (n = 4396). The whole dataset was divided into a derivation cohort (n = 1005) and validation cohort (n = 752) after excluding the patients with valvular AF and anticoagulation therapy. Using the derivation cohort dataset, a machine learning model based on gradient boosting tree algorithm (ML) was built to predict cerebral infarction. In the validation cohort, the receiver operating characteristic area under the curve of the ML model was higher than those of the existing models according to the Hanley and McNeil method: ML, 0.72 (95%CI, 0.66-0.79); CHADS2, 0.61 (95%CI, 0.53-0.69); CHA2DS2-VASc, 0.62 (95%CI, 0.54-0.70). As a conclusion, machine learning algorithm have the potential to perform better than the CHADS2 and CHA2DS2-VASc scores for predicting cerebral infarction in patients with non-valvular AF.

A Case of Treatment With Dabigatran for Cerebral Venous Thrombosis Caused by Hereditary Protein C Deficiency.

A 37-year-old woman was admitted to our hospital with involuntary movements. She had no medical or family history of thromboembolism, nor was she on any medication. She showed no impaired consciousness, cranial nerve abnormalities, abnormal breathing, stiff neck or paralysis. Magnetic resonance venography exhibited poor visualization of intracranial vein. The protein C activity level reduced but the protein C antigen level was normal. Genetic analysis revealed a heterozygous mutation in exon 7 c.577-579delAAG, p.Lys193del on protein C gene. She was diagnosed with cerebral venous thrombosis and hereditary protein C deficiency type II. She received heparin in acute phase, and switched to dabigatran in chronic phase. Consequently, she had no recurrence of cerebral venous thrombosis and other complications. Dabigatran might be one of the alternative choices for patients with cerebral venous thrombosis and protein C deficiency.

[Early Diagnosis of Spinal Dural Arteriovenous Fistula].

Spinal dural arteriovenous fistulas (SDAVF) are rare and most commonly affect men aged >50 years. Patients with SDAVF develop an abnormal vascular dural shunt between the dural branch of a segmental artery and a subdural radicular vein that drains the perimedullary venous system, leading to venous hypertension and secondary congestive myelopathy. Most SDAVFs are located in the thoracolumbar region, and usually patients present with slowly progressive paraparesis and urinary disturbances. SDAVF is diagnostically challenging; this condition may be misdiagnosed as lumbar spinal stenosis or myelitis. Clinicians should be aware of fluctuating symptoms in the early stages to avoid misdiagnosis of SDAVF. Claudication is associated with various activities including walking, bathing, drinking, and singing. On T2-weighted magnetic resonance imaging of the spinal cord, SDAVFs show a high signal intensity with a low signal intensity peripherally and dilated spinal cord veins in the subarachnoid space.

[A case of proximal-type Hirayama disease associated with neck axial rotation].

Hirayama disease is characterized by juvenile onset of unilateral muscular atrophy of a distal upper extremity. The pathogenic mechanism of Hirayama disease is cervical cord compression by the posterior dura with forward displacement in the neck flexion position. A few cases of 'proximal-type Hirayama disease' have been described as showing muscular weakness and atrophy of the proximal upper extremities caused by the pathogenic mechanism similar to that of Hirayama disease. We report herein the case of a 16-year-old boy with proximal-type Hirayama disease, who developed symptoms after he began kyudo (Japanese traditional archery). Neurological examination revealed bilateral weakness of the muscles innervated by C5 and C6 segments (the deltoid, biceps brachii, brachioradialis), bilateral mild sensory disturbance in the radial side of the forearm, absent tendon reflexes of the biceps brachii and brachioradialis with preserved triceps reflex, pyramidal signs of the bilateral lower extremities (pathologically brisk reflexes of lower extremities, Babinski's signs). MR images in the neck flexion position showing expansion of the posterior extradural space and forward displacement of the spinal cord at the C3/4, C4/5, C5/6 and C6/7 disk levels. CT myelogram revealed spinal cord compression not only in neck flexion but also in neck left axial rotation. His symptoms improved after the restriction of neck flexion and axial rotation. Weakness of the upper extremities improved after 2 months. Pyramidal signs of the lower extremities disappeared after 18 months. The pathogenic mechanism in this case may be associated with not only neck flexion but also neck axial rotation.

Pharmacological monitoring of antiepileptic drugs in epilepsy patients on haemodialysis.

To retrospectively evaluate the pharmacological profiles of antiepileptic drugs (AEDs) in epilepsy patients during haemodialysis using therapeutic drug monitoring data. The serum concentration of AEDs was collected before and after haemodialysis, and the clearance rate and concentration-to-dose ratio were calculated as pharmacological parameters. Thirty-six patients were enrolled in the study (25 males, 11 females; age: 65.3 ± 14.8 years). In 24 of the 36 patients, epilepsy was associated with cerebrovascular disorders, and diabetes was the most common reason for haemodialysis in 16 patients. With regards to seizure type, focal aware seizures were less frequent than focal impaired awareness seizures and focal-to-bilateral tonic-clonic seizures. Interictal EEG showed intermittent rhythmic slow waves and intermittent slow waves more often than spikes or sharp waves. Levetiracetam was the most commonly used AED and led to the highest percentage of responders (80%; 16/20 patients). However, the clearance rate of levetiracetam during dialysis was highest among the antiepileptic drugs used, requiring supplementary doses after haemodialysis in all 20 patients. Valproic acid was not effective for focal epilepsy for patients on haemodialysis, and non-responders to phenytoin had low serum concentration of phenytoin both before and after haemodialysis. The pre-haemodialysis concentration of levetiracetam tended to be higher than the reference range, suggesting a potential risk of overdosing before haemodialysis. The pre- and post-haemodialysis concentrations of valproic acid tended to be lower than the reference range, suggesting a potential risk of underdosing. The concentration-to-dose ratios for levetiracetam, valproic acid, phenytoin, and carbamazepine were significantly lower after than before haemodialysis. The majority of patients with epilepsy on haemodialysis had cerebrovascular diseases, and therapeutic drug monitoring for levetiracetam, valproic acid, and phenytoin, before and after haemodialysis, is needed to ensure proper dosing.

Pretreatment Blood Pressure is a Simple Predictor of Hemorrhagic Infarction after Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Therapy.

BACKGROUND: Hemorrhagic infarction (HI) is among the most severe complications that can occur following the administration of intravenous recombinant tissue plasminogen activator (rt-PA). In the present study, we aimed to determine the optimal cut-off points of blood pressure (BP) for HI after rt-PA treatment, and to compare our findings with those for other prediction models. METHODS: We analyzed data from 109 consecutive patients with stroke treated at our hospital between 2009 and 2016. HI was confirmed via computed tomography or magnetic resonance imaging. Patients were classified into a symptomatic HI group, an asymptomatic HI group, and a non-HI group. BP was measured on admission and before rt-PA treatment. Glucose Race Age Sex Pressure Stroke Severity (GRASPS) and Totaled Health Risks in Vascular Events (THRIVE) scores were also calculated. Receiver operating characteristic (ROC) analysis was used to determine factors associated with symptomatic and asymptomatic HI. RESULTS: Among the 109 total patients, 25 patients developed symptomatic HI, while 22 patients developed asymptomatic HI. ROC analysis for predicting symptomatic and asymptomatic HI revealed that the area under the curve for pretreatment systolic BP (SBP) was .88 (95% confidence interval[CI]: .83-.94), while those for GRASPS and THRIVE scores were .75 (95% CI: .66-.85) and .69 (95% CI: .59-.79), respectively. We identified an optimal cut-off point of 160 mm Hg (sensitivity: 82.3%; specificity: 76.6%; diagnostic accuracy: 80.0%; positive predictive value: 76.6%; negative predictive value: 82.5%). CONCLUSIONS: Pre-treatment SBP may be a simple predictor of symptomatic and asymptomatic HI in patients with stroke undergoing rt-PA treatment.

[Case of posterior reversible encephalopathy syndrome caused by Fisher syndrome].

This report presents a case of a 71-year-old woman with Fisher syndrome who had posterior reversible encephalopathy syndrome (PRES) before the initiation of intravenous immunoglobulin (IVIg) treatment. She had symptoms of common cold 2 weeks before the onset of PRES. On the day of the onset, she began to stagger while walking. On day 2, she developed hypertension, vision impairment, and limb weakness and was admitted to the hospital. On day 3, she was provided steroid pulse therapy. On day 4, she developed convulsions and right imperfection single paralysis and was transferred to the our hospital. During the transfer, the patient was conscious. Her blood pressure was high at 198/107 mmHg. She had mild weakness in her limbs and face, light perception in both eyes, dilation of both pupils, total external ophthalmoplegia, no tendon reflexes, and limb and trunk ataxia. We diagnosed PRES because of the high signal intensities observed on T2-weighted MRI on both sides of the parietal and occipital lobes. We also diagnosed Fisher syndrome because of a positive anti-GQ1b immunoglobulin G antibody test and albuminocytologic dissociation in the cerebrospinal fluid. PRES showed prompt improvement with antihypertensive therapy, whereas Fisher syndrome slowly improved over a course of 2 months. This case is the first report of PRES without IVIg suggesting that Fisher syndrome induces hypertension and causes PRES.

Examination of Selective Low-pressure Fine Needle Aspiration Cytology Under Ultrasound Guidance.

Cytology by fine-needle cytology is indispensable for diagnosing head and neck tumor, especially for thyroid nodule. There are two methods of fine needle cytology; one of fine-needle aspiration cytology (FNAC and another of fine-needle non-aspiration cytology (FNNAC). These previous procedures has each disadvantage such as the mixing of blood or low yield of cells. We proposed a new technique: selective low-pressure fine needle aspiration cytology (SLOP-FNAC) to overcome the backwards of previous procedures. We used the scoring system by Mair et al. to evaluate smear quality of specimens obtained with FNNAC and SLOP-FNAC. SLOP-FNAC smears exhibited higher scores in amount of cellular material, degree of cellular degeneration and cell yield, and retention of appropriate architecture compared to FNNAC smears. The SLOP-FNAC smears scored significantly higher for amount of cellular material and retention of appropriate architecture evaluated (P = 0.0261 and P = 0.0024, Student's t-test). SLOP-FNAC may be a useful cell sampling technique that reduces blood contamination while securing a high cell yield with maintaining tissue structure.

Significance of Anomalous Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery Common Trunk Compression in Microvascular Decompression for Hemifacial Spasm.

BACKGROUND: The anterior inferior cerebellar artery-posterior inferior cerebellar artery (AICA-PICA) common trunk anomaly is reportedly one of the most common vessel variants in the posterior circulation, but reports of hemifacial spasm (HFS) associated with AICA-PICA common trunk are very rare. In the present study, we describe methods of microvascular decompression (MVD) for HFS caused by AICA-PICA common trunk compression. METHODS: Among 159 patients who underwent MVD for HFS, 16 patients had compression of the root exit zone by the AICA-PICA common trunk anomaly. The types of compression were classified into 2 groups: common trunk artery compression group and branching vessel compression group. RESULTS: The common trunk artery compression group consisted of 11 patients (69%), and the branching vessel compression group consisted of 5 patients (31%). The rostral branch (feeding the original AICA territory) coursed between the seventh and eighth cranial nerves in 5 patients, and in 13 patients (81%), the offending vessel harbored perforators around the root exit zone. Among 16 patients, 14 (87.5%) required interposition of the common trunk or the branching vessel, and in 2 patients, decompression was completed by the transposition method. Fifteen patients experienced sufficient results, and 1 had severe residual spasm. Transient facial palsy developed in 2 patients. No patients encountered recurrence. CONCLUSIONS: Reports concerning decompression methods of AICA-PICA common trunk anomaly are very rare. The tortuosity of the common trunk and perforators from the offending vessel make the usual repositioning of the offending artery much more difficult, and adequate decompression techniques are required for successful MVD.

[A case of atraumatic hematomyelia extending from the C1 to T11 segments of the spinal cord].

Intramedullary spinal cord hemorrhage (hematomyelia) is rare and usually related to trauma. Spinal vascular malformations such as intramedullary cavernomas and intradural arteriovenous malformations are the most common cause of atraumatic hematomyelia. Other considerations include warfarin or heparin anticoagulation, bleeding disorders, spinal cord tumors, and delayed complication of spinal radiation. We report the case of 48-year-old man receiving warfarin and aspirin therapy, who showed upper limb pain and dysesthesia from left axilla to left femur. Paraplegia, sensory disturbance, bladder and rectal disturbance developed gradually over two weeks, accompanied by severe back and neck pain. MRI showed hematomyelia extending from the C1 to T11 segments of the spinal cord. The hemorrhage was located mainly in the left side of the posterior column. Few cases of hematomyelia extending over 18 segments of the spinal cord have been reported. Past literature reports of hematomyelia tend to extend longitudinally above and below the area of initial hemorrhage. We thought that the shape of this hematomyelia extending longitudinally over several segments was formed by a similar pathogenesis to pencil-shaped softening of the spinal cord.

[Clinical features and courses in patients with new-onset epileptic convulsive seizure: comparison of elderly with non-elderly].

We retrospectively studied the clinical features and the outcome of first acute symptomatic seizure in elderly. The subjects were 457 patients, who were more than 15 years old, and whose electroencephalograms were available in our hospital. The subjects were divided into two groups, the elderly (236 patients; age more than 60 years, mean age; 73.2±8.2, 105 female, 131 men), and non-elderly (221 patients; 15≤age≤59, mean age; 35.7±14.1, 87 female, 134 men), and were diagnosed in accordance with the guidelines of ILAE. We ascertained all episodes of acute symptomatic seizure and unprovoked seizure. Date on age, gender, etiology, status epilepticus (SE), 30-day and one-year mortalities, and subsequent episodes of unprovoked seizure were collected. Acute symptomatic seizures are more likely to occur in elderly group, and showed higher short-/and long-term mortalities than unprovoked seizures in both elderly and non-elderly groups. Acute symptomatic seizures due to multiple causes in elderly group showed the highest mortality. The outcome of patient who had SE was poorer within 30 days, but not within one year among 30-day survivors. Considering the fact that first seizures in the elderly are likely to be provoked by acute illnesses, we need to take special care in diagnosing and treating them.

[An autopsy case of progressive multifocal leukoencephalopathy: comparison of magnetic resonance imaging findings with the pathological findings].

A 41-year-old man diagnosed with malignant lymphoma (MLy) in November 2007 developed paralysis that worsened rapidly in January 2008. Magnetic resonance imaging (MRI) showed multifocal T2 high-intensity lesions without edema or gadolinium enhancement in the white matter. The lesions were characterized by a central core with low signal intensity, surrounded by a rim of high signal intensity on diffusion-weighted images (DWIs). At first, we suspected brain metastasis of MLy and used anti-cancer drugs, but the patient's condition worsened. A brain biopsy was then taken to determine whether the patient had MLy metastasis or progressive multifocal leukoencephalopathy (PML) so that an appropriate course of treatment could be determined. The biopsy contained no characteristic nuclear inclusions of PML, but we were able to rule out MLy; therefore, the patient was treated with cytarabine in February 2008, but he died because of sepsis in March. Upon autopsy, many characteristic nuclear inclusions of PML were found in the periphery of the lesions, and in the central core, there was severe demyelinating and tissue softening without typical nuclear inclusions of oligodendroglias. This structure is similar to the structure observed on DWIs, in which a low signal intensity core is surrounded by a rim of high signal intensity. The presence of inclusion bodies in the rim would correspond to the high signal intensity area on DWIs. The peripheral area may have given high signal intensity on DWIs because of the active findings of many swelling oligodendroglias with typical nuclear inclusions. Conversely, the central lesions would give low signals on DWIs because of demyelination and softening. Hence, the region with high signal intensity adjacent to the central low signal area on DWIs would be an appropriate biopsy point for PML diagnosis. ).

[Case report of nocardia brain abscess that needs to be distinguished from metastatic brain tumor].

We report a 62-year-old woman presenting with nocardia brain abscess that mimics metastatic brain tumor. Six months before admission to our hospital, she presented with persistent hemoptysis, and a friable endobronchial mass was detected at another hospital. However, a definite diagnosis had not been made, and then she presented with hemianopia. Her laboratory analysis results showed that she had no immunological abnormalities. T1-weighted magnetic resonance images of the brain with Gd-DTPA revealed hyperintensive multiple masses with surrounding edema. We suspected this case as metastatic brain tumor of unknown origin, and the patient underwent biopsy of the supraclavicular lymph node. Histopathology results indicated abscess, and gram staining of material obtained from the abscess showed Gram-variable rods, which were determined upon culture as acid-fast Gram-positive branching rods and identified as Nocardia asteroides. Accordingly, we diagnosed the patient as having nocardia brain abscess, and she was treated with an oral antibiotic (TMP-SMX). Four months later, the abscesses disappeared. The patient recovered after prolonged TMP-SMX therapy with no recurrence in over 9 months.

Alpha-amylase production is induced by sulfuric acid in rice aleurone cells.

The hydrolytic enzyme alpha-amylase (EC 3.2.1.1) is produced mainly in aleurone cells of germinating cereals, and the phytohormone gibberellin (GA) is essential for its induction. However, in rice (Oryza sativa L.), sulfuric acid (H(2)SO(4)) induces alpha-amylase production in aleurone tissue even in the absence of GA. Here, the pre-treatment of rice aleurone cells with H(2)SO(4) and incubation in water induced alpha-amylase activity, as if the cells had been incubated in GA solution.

Skull bone regeneration in nonhuman primates by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel.

The objective of this study was to investigate the feasibility of biodegradable gelatin hydrogels as the controlled-release carrier of bone morphogenetic protein-2 (BMP-2) to enhance bone regeneration at a skull defect of nonhuman primates. Hydrogels with 3 different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. A critical-sized defect (6 mm in diameter) was prepared at the skull bone of skeletally mature cynomolgus monkeys, and gelatin hydrogels incorporating various doses of BMP-2 were applied to the defects. When the bone regeneration was evaluated by soft radiography and bone mineral density (BMD) examinations, the gelatin hydrogel incorporating BMP-2 exhibited significantly higher osteoinduction activity than did an insoluble bone matrix that incorporated BMP-2 (one of the best osteoinduction systems), although the activity depended on the water content of hydrogels. BMD enhancement was highest for the gelatin hydrogel that had a water content of 97.8 wt% among all types of hydrogels. Moreover, the gelatin hydrogel enabled BMP-2 to induce the bone regeneration in nonhuman primates even at low doses. We conclude that the controlled release of BMP-2 for a certain time period was essential to inducing the osteoinductive potential of BMP-2.

Acceleration of aneurysm healing by hollow fiber enabling the controlled release of basic fibroblast growth factor.

OBJECTIVE: The objective of this study was to develop an embolization material of hollow fiber combined with gelatin hydrogel for the controlled release of basic fibroblast growth factor (bFGF). We examined feasibility of the material in embolization healing aneurysm by bFGF-induced tissue organization. METHODS: An aneurysm was prepared at the common carotid artery of 60 rabbits by the end-to-side anastomosis of jugular venous pouch. The hollow fibers combined with or without 100 microg free bFGF or gelatin hydrogel incorporating 0, 10, 50, or 100 microg bFGF were applied to the aneurysm. Tissue appearance or histological observation was performed 1, 2, 3, and 6 weeks after application to evaluate the area embolized by fibrous organization in the aneurysm and the neointima formation at the aneurysm orifice. RESULTS: When applied with the hollow fibers combined with gelatin hydrogel containing 100 microg bFGF, the aneurysm was histologically occupied by fibrous tissue newly formed 3 weeks later, whereas neointima was formed at the aneurysm orifice. The histological area occupied by fibrous tissue was significantly larger than that of hollow fibers combined with 100 microg bFGF. No influence of bFGF dose on the aneurysm healing by the fibers combined with hydrogels incorporating bFGF was observed. CONCLUSION: Local, controlled release of bFGF from the hollow fibers combined with gelatin hydrogel incorporating bFGF accelerated the aneurysm healing by tissue organization.

Augmented bone regeneration activity of platelet-rich plasma by biodegradable gelatin hydrogel.

This study investigates the ability of platelet-rich plasma (PRP) combined with biomaterials to enhance in vivo bone-repairing activity. A biodegradable hydrogel was prepared from gelatin, which has an affinity for various growth factors. Rabbit PRP was conventionally prepared by blood centrifugation and dropped onto freeze-dried gelatin hydrogel to obtain gelatin hydrogel incorporating PRP. Gelatin hydrogel incorporating PRP was applied to a bone defect of rabbit ulna to evaluate bone formation at the defect in terms of soft X-ray and histological examinations. As controls, fibrin incorporating PRP, empty gelatin hydrogel, and free PRP were applied to the defect; in addition, defect without any application was examined. Successful bone regeneration was observed at bone defect treated with gelatin hydrogel incorporating PRP, in marked contrast to the control groups. When in contact with gelatin, growth factors, such as platelet-derived growth factor and transforming growth factor beta(1), were released from the PRP. PRP growth factors are immobilized in the hydrogel through physicochemical interaction with gelatin molecules. The immobilized growth factors are released from the hydrogel in concert with hydrogel degradation. It is likely that the gelatin hydrogel permitted the controlled release of bioactive growth factors, resulting in factor-induced promotion of bone regeneration.