Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Convergent validity evidence for the Pain and Discomfort Scale (PADS) for pain assessment among adults with intellectual disability.

OBJECTIVES: The main aim of the study was to generate initial convergent validity evidence for the Pain and Discomfort Scale (PADS) for use with nonverbal adults with intellectual disabilities. MATERIALS AND METHODS: Forty-four adults with intellectual disability (mean age=46, 52% male) were evaluated using a standardized sham-controlled and blinded sensory testing protocol, from which Facial Action Coding System (FACS) and PADS scores were tested for (1) sensitivity to an array of calibrated sensory stimuli; (2) specificity (active vs. sham trials); and (3) concordance. RESULTS: The primary findings were those participants who were reliably coded using both FACS and PADS approaches as being reactive to the sensory stimuli (FACS: F(2,86)=4.71, P<0.05, PADS: F(2,86)=21.49, P<0.05) (sensitivity evidence), not reactive during the sham stimulus trials (FACS: F(1,43)=3.77, P=0.06, PADS: F(1,43)=5.87, P=0.02) (specificity evidence), and there were significant (r=0.41 to 0.51, P<0.01) correlations between PADS and FACS (convergent validity evidence). DISCUSSION: FACS is an objective coding platform for facial expression. It requires intensive training and resources for scoring. As such it may be limited for clinical application. PADS was designed for clinical application. PADS scores were comparable with FACS scores under controlled evaluation conditions providing partial convergent validity evidence for its use.

Evaluating a sham-controlled sensory-testing protocol for nonverbal adults with neurodevelopmental disorders: self-injury and gender effects.

UNLABELLED: Ambiguous or blunted responses to sensory and painful stimuli among individuals with severe intellectual disabilities and comorbid communicative impairments put them at risk for having their experience of pain discounted and their expression of pain misinterpreted. Valid measurement procedures of behavioral expression are critical for this vulnerable group of individuals. We investigated a sham-controlled sensory-testing protocol as an approach to guard against observer bias during nonverbal behavioral recording for individuals with intellectual disabilities. Participants were 44 (52% male) adults (mean age = 46, sd = 10) with moderate (14%) and severe to profound (86%) intellectual impairment. The facial behavior of the participants before, during, and after 5 sensory-stimulation modalities (pin prick, light touch, deep pressure, cool, warm) was coded by 3 raters using the Facial Action Coding System (FACS). For each participant, the 5 active sensory trials were randomized with sham trials during which no stimulation was applied. Observers were blinded to active vs sham stimulation status. FACS scores increased significantly during active sensory trials (P < .05) compared with sham trials. There were significant effects for gender, with females more expressive than males (P < .05). There were also significant effects for the presence of self-injurious behavior (SIB), with individuals with SIB more expressive than individuals without SIB (P < .05). The results suggest that the procedure was valid (ie, distinguished between active vs sham sensory stimulation) and provides additional evidence that individuals with significant intellectual impairments are sensitive to tactile stimulation consistent with quantitative sensory-testing protocols. PERSPECTIVE: This article presents a novel application of a modified approach to quantitative sensory testing for nonverbal adults with intellectual and developmental disabilities. This approach could be important in helping determine sensory issues related to tactile and nociceptive processes among a highly vulnerable group of individuals.

Continuous decompression using a cannulated ceramic pin for simple bone cysts.

PURPOSE: To report the outcomes of continuous decompression using a cannulated ceramic pin for simple bone cysts (SBCs). METHODS: Seven boys and 3 girls aged 7 to 16 (mean, 11) years with SBCs underwent curettage and continuous decompression using a cannulated ceramic pin. The pin was made of hydroxyapatite and tricalcium phosphate. The clinical course, radiological findings, and complications were retrospectively assessed. RESULTS: The mean follow-up duration was 41 (range, 12-84) months. Five patients were evaluated as 'healed', 2 as 'healing with defect', one as 'persistent cyst', and 2 as 'recurrent cysts'. No peri-operative complications were encountered. One patient had a postoperative fracture at the pin insertion site. Seven patients had pain relief and good outcomes; 2 had a thin cortical rim and complained of occasional pain and their sports activities were restricted. CONCLUSION: Decompression using a cannulated ceramic pin for SBCs is minimally invasive, highly osteoconductive, and does not require bone grafting or a second operation to remove the device.

Short-term complications and long-term results of expansive open-door laminoplasty for cervical stenotic myelopathy.

BACKGROUND CONTEXT: Laminoplasty has been reported to achieve good operative results for treatment of cervical stenotic myelopathy. However, long-term results and prognostic factors have not been well documented. Among postoperative complications, weakness of the shoulder girdle muscles has been reported as a particular complication of laminoplasty, but the cause is still poorly understood. PURPOSE: Our aim was to clarify the short-term complications and long-term operative results after unilateral open-door laminoplasty and to identify the predictors for operative outcome. STUDY DESIGN: We retrospectively reviewed short-term complications and long-term operative results associated with cervical stenotic myelopathy treated by unilateral open-door laminoplasty. PATIENT SAMPLE: There were 162 men and 42 women with an average age of 57 years who were treated by unilateral open-door laminoplasty in the two institutions. Pathogenesis of myelopathy was cervical spondylosis in 88 patients, cervical disk herniation with a narrow spinal canal in 10, and ossification of the posterior longitudinal ligament in 106. OUTCOME MEASURES: Postoperative complications and their outcomes were examined clinically in 204 patients, and causes of motor paresis were sought with postoperative computed tomography after myelography. Postoperative improvement of clinical symptoms was assessed by recovery rate calculated with the scores of the Japanese Orthopaedic Scoring System in 80 patients. METHODS: The occurrence rate of short-term postoperative complications, causes of motor paresis, and their outcomes were reviewed in 204 patients. Clinical condition was assessed with the Japanese Orthopaedic Scoring System, recovery rate was calculated with the score, and prognostic factors for outcome were studied in 80 patients who were followed up for 5 years or longer (average, 8 years; range, 5-17 years). RESULTS: Occurrence rate of complications, such as muscle weakness, deep infection, closure of opened laminae, and others, was 10.8%. Muscle weakness was observed in 7.8% of the patients. However, this rate decreased in recent years. The cause of motor paresis is not known with certainty, but it may be secondary to operative trauma, posterior shift of the spinal cord, or to displacement of the lamina in the hinge side. Recovery rate of clinical symptoms was 62.1% at the final follow-up. Rates were 63.6% for cervical spondylosis, 87.1% for cervical disk herniation, and 61.3% for ossification of the posterior longitudinal ligament. There was no significant difference between pathologies. Patient age younger than 60 years at the time of operation and less than 1 year's duration of symptoms before surgery were significantly associated with recovery rate of clinical symptoms. Recovery rate was not correlated with either preoperative function judged by the Japanese Orthopaedic Association score or spinal sagittal diameter. CONCLUSIONS: The main cause of postoperative motor paresis of upper extremities is thought to be operative trauma, resulting from such procedures as air-drill and Kerrison rongeur handling. Short-term complications may decrease with the use of nontraumatic procedures. Better operative outcomes may be achieved with careful operative procedures and early operative treatment in the patients with myelopathy.

Blood biochemical characteristics, cecal microbiota and short-chain fatty acid composition in fistula implanted rats.

We raised an experimental rat implanted with a cecal fistula and investigated various characteristics of fistula-implanted rats. Male F344/N Sic rats at 14 weeks of age were divided into three groups, the fistula group (n = 5) which consisted of fistula-implanted rats, the sham group (n = 7) which consisted of sham-operated rats, and the control group (n = 7) which were not subjected to any surgical procedure. Four weeks after the fistula implantation surgery, we compared the blood biochemical indices, the microflora composition and the short-chain fatty acids (SCFA) concentration in cecal contents of fistula-implanted rats with those of sham-operated and control rats. The blood albumin concentration of the fistula group was significantly lower than that of the sham group and the control group, and the hematocrit value of the fistula group was significantly lower than that of the control group, but there were no significant differences in the SCFA concentration and the microflora composition among these three groups. In conclusion, it was considered that the fistula-implanted rats are useful for taking cecal contents and determining the microflora composition and the metabolites concentration at any time, without disturbing the physiological functions of the intestinal tract.

[Effectiveness of continuous intravenous prostaglandin E 1 against pulmonary hypertension].

Pulmonary hypertension is a progressive disease for which no effective therapy has been found. Short-team treatment with alprostadil alfadex (PGE 1) can improve hemodynamics but the effects of long-term treatment have not been reported. We administered intravenous PGE 1 to 16 patients with pulmonary hypertension for 4 weeks in addition to conventional therapy. Hemodynamic and symptomatic effects were evaluated. The infusion was interrupted in 7 patients (44%) because of fever and an increase in levels of C-reactive protein in serum. In the remaining 9 patients, the drug lowered pulmonary artery pressure and resistance, and imareased cardiac output significantly in 7 patients. PGE 1 can improve hemodynamics and relieve symptoms in patients with pulmonary hypertension, barring severe side effects.

[Recurrent pneumomediastinum in the course of interstitial pneumonia associated with dermatomyositis].

A 59-year-old woman with dermatomyositis suffered pneumomediastinum twice during steroid therapy for aggravated myositis. In both instances, pneumomediastinum occurred when the patient's aggravated myositis was in remission. Plain chest X-ray films showed a slit-like air lucency around the left pulmonary artery. This indicated that air entered the mediastinum through the left hilum. Although pneumomediastinum associated with dermatomyositis is considered to be fatal, in our patient each instance of pneumomediastinum spontaneously disappeared very quickly. The favorable course of our patient seemed to be associated with her high elevated levels of serum creatine kinase and seropositive results for anti-Jo-1 antibody.

Fecal microflora in a patient with short-bowel syndrome and identification of dominant lactobacilli.

Fecal microflora and lactate concentrations in blood and feces obtained from a patient (a 5 year-old boy) with short-bowel syndrome (SBS) were compared during acidosis to results for the normal condition (no SBS symptoms). The taxonomical position of the lactobacilli found predominantly in the feces sample obtained 2 days before the fifth attack was also studied. The D-lactate level in serum obtained 1 day after the fourth attack was 10-fold higher than that for the normal condition, although there was not a great difference in L-lactate levels. D-Lactate (3.91 mM) and L-lactate (2.86 mM) were also detected in the feces samples collected 2 days before the fifth attack, while no lactate was detected in the feces sample for the normal condition. The counts of total fecal bacteria, especially anaerobic bacteria such as members of the family Bacteroidaceae, were found to be low. The counts of lactobacilli and the total population of lactobacilli relative to total fecal bacteria in the feces 2 days before the fifth attack (40.4%) were extremely high. In this case, a majority of the lactobacilli were D-lactate producers as determined by homolactic fermentation. These lactobacilli were identified as Lactobacillus delbrueckii subsp. lactis. The percentages of bifidobacteria relative to total fecal bacteria in feces samples obtained both 2 days before the fifth attack (50.9%) and for normal condition (61.9%) were also high, although these bacteria were L-lactate producers. In the feces samples for the normal condition, the D-lactate producers decreased to less than 10(9) per g, while the counts of L- or DL-lactate producers were 100-fold higher than the numbers in feces samples obtained 2 days before the fifth attack. These results suggested that an increase in the level of D-lactate producers, such as L. delbrueckii subsp. lactis, in the colon may be associated with the clinical expression of metabolic acidosis.

Management of patients with an incomplete cervical spinal cord injury.

Forty-five patients with incomplete cervical spinal cord injuries were examined as to the mechanism of injury, neurological deficits in the initial stage and differences in treatment. Nineteen (42.2%) were treated non-surgically and 26 (57.8%) surgically. Their injuries could be divided into seven types of cervical spinal cord injury according to Usui's classification. Neurological changes were evaluated with Frankel's grading system. The neurological prognosis was relatively better in those with a unilateral cord injury type, but there was no statistical difference. Thirty-seven patients (82.2%) showed neurological improvement of at least one Frankel grade. There was no statistical difference between the surgical and non-surgical groups regarding neurological improvement, but all who underwent early surgery (within 4 weeks of being injured) improved. Surgical treatment was considered to be indicated for patients with cervical spinal canal narrowing, when satisfactory neurological improvement is not obtained by conservative treatment.

Hemispheric asymmetry of event-related potentials in a patient with callosal disconnection syndrome: a comparison of auditory, visual and somatosensory modalities.

To investigate whether callosal lesions affect the distribution of event-related potentials (ERP) between the two hemispheres and whether hemispheric ERP distribution differs among sensory modalities, a patient with interhemispheric disconnection syndrome and 47 controls were subjected to an oddball paradigm. High (target) and low tone bursts for auditory, red (target) and green lights for visual and electrical stimuli delivered to the index (target) or fifth finger for somatosensory ERPs were presented to the unilateral ear, visual field and hand, respectively. The subjects were instructed to press a button with the hand on the stimulated side. The results showed that the hemispheric asymmetry of the patient's auditory ERPs was not significantly different from that of the controls, regardless of which ear was stimulated. In contrast, the visual and somatosensory ERPs showed a delay of the P3 latency and an attenuation of the N1-P2 and N2-P3 amplitude over the hemisphere ipsilateral to the stimulus, regardless of the stimulated side. These findings suggest that the source of P3 generation is relatively lateralized to the hemisphere contralateral to the stimulus, and that the callosal transfer of visual and somatosensory information is involved in the P3 generation in the hemisphere ipsilateral to the stimulus.

Long-term follow-up studies of open-door expansive laminoplasty for cervical stenotic myelopathy.

Follow-up at an average time of 7.8 years postoperatively on open-door expansive laminoplasty (EL) was carried out to determine the long-term results of surgery. Thirty-three patients had ossification of the posterior longitudinal ligament and 18 had cervical spondylotic myelopathy. The average age at operation was 54.7 years. Japanese Orthopaedic Association scores and recovery rates increased during the 3 years after surgery and then plateaued. Radiographically, average spinal canal diameter remained enlarged past 5 years' follow-up. Factors leading to worsening of clinical symptoms included age greater than 60 years (4 patients), loss of sagittal canal diameter (2 patients), progression of ossification (4 patients), and minor trauma (1 patient). Postoperative motor paresis due to C5 and C6 root damage recovered to 4 (manual muscle testing) in all patients within 6 years. The conclusion is that open-door EL is safe and leads to good results that are maintained for over 5 years.

Posterior fracture-dislocation of the thoracic spine without neurologic deficit. A case report and short literature review.

The authors present a case of posterior fracture-dislocation of the thoracic spine without neurologic deficit. A 63-year-old man injured by traffic accident. His spinal fracture-dislocation was treated conservatively because of his complications. At the present time, approximately 1 year after the injuries, the patient does not have any neurologic complaint. Conservative treatment should be adopted as the first choice in patients at older ages and in those with underlying diseases or serious complications.

Predictability of operative results of cervical compression myelopathy based on preoperative computed tomographic myelography.

The transverse area and flattening ratio of the spinal cord were determined with preoperative computed tomographic myelography in 103 patients with cervical compression myelopathy: cervical spondylotic myelopathy (n = 44); ossification of the posterior longitudinal ligament (n = 39); and cervical disc herniation (n = 20). With these values and other clinical items (eg, age, duration of symptoms, preoperative severity), a linear model to predict postoperative recovery was attempted by multiple regression analysis. In cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament, the transverse area of the spinal cord and the duration of symptoms were accepted as effective explanatory variables to predict recovery. In cervical disc herniation, regardless of the transverse area or duration, the recovery was good, and pathologic state was considered essentially different.

Idiopathic spinal cord herniation. Report of two cases and review of the literature.

The authors experienced unique cases of spinal cord herniation. Only eight cases of spinal cord herniation have been reported formerly. The authors report two cases of spinal cord herniation accompanied with double structure of dura mater (duplicated dura mater). The causes of their condition are discussed in this report.

Electrophysiological study of superficial abdominal reflexes in normal men.

We studied the superficial abdominal reflexes of 83 normal men, using as stimuli a train of electrical pulses or a needle scratch. Electrical stimulation delivered to the midline of the abdominal wall evoked, almost symmetrically on both sides, two reflex discharges: an early response having an oligophasic wave form, and a late response of polyphasic wave form. The threshold of the early response significantly exceeded that of the late response. With repetitive stimulation, the late response generally revealed habituation. Electrical stimulation of the unilateral abdominal wall evoked two responses on the stimulated side, whereas it evoked only the late response on the contralateral side. A needle scratch on the unilateral abdominal wall evoked one reflex discharge with a long latency and a polyphasic wave form. This response occurred generally on the stimulated side and became habituated to repeated scratching. These observations suggest that the superficial abdominal reflexes elicited by electrical stimulation are composed of two reflex discharges with a different reflex arc. They appear to closely resemble the blink reflex. The response elicited by needle scratching is thought to correspond to the late response of the electrically elicited abdominal reflexes.

A clinical study of degenerative spondylolisthesis. Radiographic analysis and choice of treatment.

Surgical treatment of degenerative spondylolisthesis in 27 patients by means of anterior lumbar interbody fusion and in 14 patients by means of posterior decompression yielded average degrees of recovery of 77% and 56%, respectively. Preoperative analysis of myelograms, and computed tomographies after myelography indicated that anterior shifting of the inferior articular process of the slipping vertebra was the main factor responsible for compression of the nervous tissue in the early stages of degenerative spondylolisthesis. Patients in these stages should be treated by anterior lumbar interbody fusion. In the later stages of degenerative spondylolisthesis, osteophytes on the superior articular processes of the lower vertebra were an additional factor in compression, and patients should be treated by posterior decompression. Computed tomographies after myelography provided the key images for identifying pathologic processes in degenerative spondylolisthesis and selecting appropriate surgical procedures.

Spontaneous fracture of the odontoid process in rheumatoid arthritis.

Six cases of spontaneous fracture of the odontoid process in rheumatoid arthritis are presented. Fifty-one patients with atlantoaxial subluxation in rheumatoid arthritis underwent surgery between 1981 and 1990. This included six patients (in 10%) who had subluxation accompanied by fracture of the odontoid without apparent trauma. The mean patient age was 58 years and all had a long history of rheumatoid arthritis. No trauma was considered to be the cause of the fracture. This is a fracture caused by erosion and osteoporosis of the odontoid process due to rheumatoid synovitis, aging and steroid therapy. In addition, another cause is a dynamic load produced from the instability accompanying atlantoaxial subluxation working on the odontoid in cervical extension. It is important remember that the odontoid process is susceptible to spontaneous fracture.